Aspergillus species. These toxins are frequently detected in food and feed and impose either acute or chronic effects in humans and animals, causing great public concern. Because of the adverse effects of aflatoxins, many physical, chemical, and biological decontamination approaches have been developed. However, the most commonly used procedure is the addition of adsorbent materials into aflatoxin-contaminated diets to reduce toxin absorption and distribution to blood and target organs. In recent times, sorption technology with agro-waste-based materials has appeared as a promising alternative over conventional binding agents with the benefits of low cost, higher rentability, feasibility, and exceptional efficiencies. This review is mainly focused on discussing the most important agro-waste-based materials able to adsorb aflatoxins such as pomaces, seeds, stems, hulls, peels, leaves, berries, lignins, fibers, weeds, and various horticultural byproducts. Further data of the in vitro, in vivo, and in silico efficacy of these biomaterials to adsorb and then desorb aflatoxins are given. Besides, an overview of the main characterization techniques used to elucidate the most important physical and chemical mechanisms involved in the biosorption is presented. Finally, conclusions and future research necessities are also outlined.Aflatoxins are the most hazardous fungal-generated secondary metabolites produced by toxigenic  Mycotoxins are a group of low molecular weight substances synthesized during the secondary metabolism of toxigenic fungi. These metabolites vary from simple compounds like moniliformin to very complex chemical structures such as the macrocyclic hexapeptide mycotoxins . Up to nAspergillus section Flavi (Aspergillus togoensis synthesize aflatoxin B1 (AFB1) only; A. flavus and A. pseudotamarii synthesize aflatoxin B1 (AFB1) and aflatoxin B2 (AFB2); while A. aflatoxiformans, A. arachidicola, A. austwickii, A. cerealis, A. luteovirescens, A. minisclerotigenes, A. mottae, A. nomius, A. novoparasiticus, A. parasiticus, A. pipericola, A. pseudocaelatus, A. pseudonomius, A. sergii, and A. transmontanensis produce AFB1, AFB2, aflatoxin G1 (AFG1), and aflatoxin G2 (AFG2)  have been classified as carcinogenic to humans (Group 1) by the International Agency for Research on Cancer  . AFB1 hagenicity ; consequn Cancer . As manyin vitro and in vivo  is the largest fruit crop in the globe. In 2019, the grape production was over 98 million tons per year; about eighty percent was used in the winemaking industry, and the rest was for the preparation of juice, jams, and raisins . The maximum adsorption value recorded for AFB1 was 82% , and aflatoxin adsorption was significantly affected by the adsorbent dosage, the percentage of mycotoxins removed from neutral pH increased with increasing dosages of the biosorbent. By using the Langmuir model, the authors theoretically estimated the C50 (the adsorbent dosage to accomplish a 50% reduction of the toxin); thus, the C50 value for AFB1 was 1.2 mg/mL. Five years later, in another study from the same research group, Greco et al. , artichoke, plantain peels, almond hulls, and carobs . In general, byproducts obtained from grapefruits (seeds and pomaces) adsorbed most aflatoxin. The mycotoxin-binding efficacy of grape pomaces is mainly related to the presence of micronized fibers and phenolic compounds. As the pH influences, the interaction between mycotoxin and biosorbent, Greco et al.  were tested in buffer solutions containing aflatoxins . Significant AFB1 adsorption efficiencies were observed (olive pomace 74% and grape stems 96%) in all tested pHs . In general, 30 mg/mL of olive pomace and 10 mg/mL of grape stems were necessary to achieve substantial adsorptions. Regarding desorption studies with buffer at pH 7, olive pomace was the biomaterial with the lowest capacity to retain the mycotoxin since desorption for AFB1 was as high as 40%. Grape stems retained the mycotoxin better; AFB1 was released only in a small amount, <5%  on productive parameters, plasma levels, liver damage, and intestinal tissues of pigs after weaning. The inclusion of grape seed in the aflatoxin-contaminated diet (8% w/w) enhanced the phase-I antioxidant enzymes activity, restored the pro-inflammatory cytokines and thiobarbituric acid reactive species (TBARS) levels, and improved the growth performance of the AFB1-intoxicated pigs (1 in pigs at higher inclusion levels (without adverse side effects). Unfortunately, the in vivo efficacies of olive pomace and grape stems have not been confirmed yet.Grape  is considered the world's fourth most important agricultural crop, with a worldwide production of about 102 million tons per year  at a concentration of 0.5 μg/mL of each toxin. In general, oven-dried banana peel was found to be more effective in removing aflatoxins. The optimum adsorbent dosage was 60 mg/mL, and most of the adsorption occurred in 10 min, while the maximum was reached in 30 min. The sorption capacity of banana peel increased with increasing pH (from 3 to 9). At pH 8, the maximum adsorption uptakes for AFB1, AFB2, AFG1, and AFG2 were 74.9, 63.1, 76.1, and 92.8%, respectively . This considerable variation in the efficiency of the biomaterial might be mainly due to the adsorbent dosage, the differences in banana species/cultivar, the maturity stage, the feed matrix effect, the consecutive incubation periods at different pHs, as well as the enzymatic activities utilized in the multi-compartmental model. In general, the efficacy of banana peel in removing aflatoxins is related to the presence of surface functional groups, the heterogeneous microstructure, and pigment content . Further in vitro studies regarding toxin desorption and in vivo trials to evaluate the effectiveness of banana peel, however, need to be conducted.Banana  Rehder] is a spiny perennial shrub endemic in Taiwan. In many parts of the world, this one and some related species of the Rosaceae family are cultivated for decorative and walls purposes. Commonly, this plant is used in conventional medicine due to the diuretic, cardiac, and stimulant properties of its berries  in samples contaminated with 100 ng B-aflatoxins/mL. In the experiment, the ratio of AFB1 to AFB2 tested was 7:3, and adsorption was evaluated at 40°C up to 24 h. In general, the highest aflatoxin adsorption values were 86 and 82% using leaves and the combination of leaves and berries, respectively. A modest biosorption uptake (46%) was reported when using berries . All conditions used in the adsorption experiments were identical to those described in section Banana Peel. Using this multi-compartmental model, the authors indicated that the efficacy of the biomaterial was moderate; the biosorption uptake achieved was 46% , Méndez-Albores et al. ; thus, the authors suggested that carboxylate ion-enriched adsorbents could be a very good option for AFB1 removal in in vitro and in vivo trials.Formosa firethorn [ berries ; howevertic dyes –30. To da et al.  reported berries . Unfortu berries , using a was 46% . Howevers et al.  showed tin vivo studies demonstrate the effectiveness of dietary lignin in alleviating the adverse effects of deoxynivalenol and zearalenone in broiler chickens  and lignins from the wood of spruce Pícea using an in vitro setup simulating the operational conditions of the digestion in the stomach of animals. In the experiment, the sorbents were utilized at 0.1% (w/v) in samples spiked with 1 μg AFB1/mL, which were incubated at 37°C for 30 min at pH 2. In general, lignins from R. tomentosum and A. officinalis exhibited the highest AFB1-adsorption capacities. In these samples, the AFB1-uptakes reached 79.6 and 80.2%, respectively (Atriplex patula presented the lowest ability to adsorb AFB1 (up to 41%). Furthermore, desorption studies conducted at pH 8 confirmed that lignins from R. tomentosum and A. Officinalis adsorbed irreversible the mycotoxin (<5.3% desorption). The selectivity of certain functional groups (OH) and the capillary-porous structure of lignins were responsible for their strong association with the AFB1 molecule. Although lignins have been proven in vivo to be effective in alleviating the adverse effects of deoxynivalenol, zearalenone, and T-2 toxin, there are no reports of their use in reducing the negative effects of aflatoxins using in vivo models. Furthermore, micronized fibers consisting mainly of cellulose, hemicellulose, and lignin, have also been reported as effective mycotoxin binders. It has been reported that micronized wheat fibers (up to 2% inclusion in diet) decrease the levels of ochratoxin-A in plasma, kidney, and liver of piglets and rats  peel for the adsorption of AFB1. Higher adsorption efficiency toward AFB1 (98.4%) was found for this biomaterial  is a drought-resistant plant of the Liliaceae family. This plant has been used for medicinal purposes for over 5,000 years. Aloe vera gel is the mucilaginous extract of the leafy pulp, which is usually separated by scratching. It is well-known that the gel contains many phytochemicals  and has been claimed to have several curative and therapeutic properties . In general, Aloe vera powder limited the availability of AFB1 in the intestinal segment up to 69%  wastes and field horsetail (Equisetum arvense L.) in removing AFB1. The adsorption of AFB1 (190 ng/mL) was explored at two sorbent contents (0.5% and 0.1% w/v) and three pHs . Adsorption was carried out at 40 °C for 2 h . However, at 0.1% (w/v), lettuce showed the highest ability against AFB1 removal, the AFB1 biosorption percentage was 95% . Adsorption was mainly due to the interaction of the AFB1 molecule with the functional groups of the biosorbents as well as to the formation of AFB1-chlorophyll complexes. Thus, the authors concluded that lettuce wastes could have significant potential for the removal of AFB1 in some gastrointestinal tract compartments at low inclusion levels. One year later, in another study by the same research group, Vázquez-Durán et al. (Brassica oleracea L.) using a dynamic in vitro model that simulated the conditions of the gastrointestinal tract of poultry. The biosorbent was added to a contaminated poultry feed (100 μg AFB1/kg) at a content of 0.5% (w/w). According to the adsorption results, the maximum adsorption capacity of kale was 93.6% in the intestinal section  and electrostatic interactions (ionic attractions). In addition, the authors also concluded that the formation of AFB1-chlorophyll complexes improved the rate of AFB1 adsorption. However, as recommended by Ramales-Valderrama et al.  Areschoug to remove AFB1. The study was conducted using two models, one in vitro and the other in vivo; the latter focused on evaluating the capacity of the adsorbent to prevent the toxic effects of AFB1 in broilers. The adsorption of AFB1 (1 μg AFB1/mL) was explored in vitro at four sorbent contents  and two pHs (3 and 6). In general, highest percentages of AFB1 removal were achieved at a content of 0.2% in both evaluated pHs. In these samples, the AFB1-uptakes reached 77.6 and 77.4%, respectively  improved productive parameters , reduced the relative weight of the liver and the macroscopic and microscopic changes caused by the AFB1 intoxication, and improved some biochemical parameters in birds that received a diet contaminated with 1,018 μg AFB1/g feed  on the x-axis and intensity on the y-axis. Intensity could be measured both in transmittance or absorbance modes. In the literature reviewed, most of the spectra were collected to recognize the main functional groups of the tested biosorbents. However, in the work of Ramales-Valderrama et al.  or a change in the band intensity confirm the involvement of a specific functional group in the aflatoxin binding. 1 molecule  may be expected to improve the rate of AFB1 uptake by the biosorbents containing significant amounts of chlorophylls (The UV-Vis diffuse reflectance spectroscopy (DRS) is a useful technique for the characterization of biomaterials. Diffuse reflectance occurs as UV-Vis-light enters the sample, interacts with its components, and scatters backward. As a consequence, this technique provides information related to structural, physical, and chemical properties of the biomaterials and offers exceptional versatility because of its high sensitivity. Diffuse reflectance measurements make it possible to quickly and non-destructively evaluate—sorbents . Zavala-sorbents  and Vázqsorbents  found throphylls , 25.in vivo.The adsorption of mycotoxins to a biomaterial surface in aqueous media could be based on a set of chemical and physical mechanisms, including hydrogen bonding, electrostatic attraction, ion exchange, chelation, precipitation, complexation, among others. Apparently, electrostatic interaction is the most important phenomenon during mycotoxin adsorption. Thus, zeta potential is important for the characterization of electrochemical surface properties since the electrokinetic potential at the electrical double layer is associated with the surface charge of colloidal suspensions. Both surface charge and environmental conditions—pH and ions in the medium—influence the zeta potential. Commonly, the zeta potential is determined by the micro-electrophoresis technique. In this procedure, a voltage is applied across a pair of opposite gold-plated electrodes; as a result, charged particles are attracted to the oppositely charged electrode and their velocity measured. The SI unit for electrophoretic mobility is μm cm/V s, since it is a velocity (μm/s) per field strength (V/cm). The electrophoretic mobility is the direct measurement from which zeta potential can be derived using the Helmholtz-Smoluchowski, Debye-Hückel, or Henry functions. Biosorbents with a zeta potential value between −10 and +10 mV are neutral, while those with zeta potentials >+30 mV or <-30 mV are strongly cationic or strongly anionic, respectively. In the literature, various research groups have reported the zeta potential of different biosorbents used for the removal of mycotoxins , 22, 39.in vitro adsorption of aflatoxins. Most of the biomaterials summarized in in vitro, but none of them have confirmed their effectiveness in in vivo trials. Considering the pH in the different compartments of the gastrointestinal tract of poultry, biosorbents with low pHpzc could be the most suitable to be used for the adsorption of aflatoxins when using in vivo models. Consequently, it would be interesting to study the in vivo effectiveness of the modified sugar beet pulp waste to remove aflatoxins since this biomaterial has the lowest pHpzc reported in the literature.The point of zero charge (pHpzc) gives useful information about the surface charge of the biosorbents. It is well-known that pH influences sorption, mainly because pH governs the ionization of functional groups. In consequence, the pH at which the sorbent surface charge become equal to zero is defined as the point of zero charge. In other words, the charge of the positive surface sites is equal to that of the negative ones. It has been suggested that if pH < pHpzc, the surface of the biomaterial will be positively charged, and if pH > pHpzc, the surface will be negatively charged . Several1. The authors found that the main elements of banana peel, Pyracantha leaves, and Aloe powder were C and O, corresponding to 97.3, 99.2, and 85.7% of the total weight, respectively. They also observed other minor elements such as Na, Mg, Al, Si, P, S, Cl, K, and Ca. Adunphatcharaphon et al.  can be accomplished by SEM. When scanning electron microscope is accessorized with EDS, chemical microanalysis can also be conducted with 1–3% accuracy  is one of the most versatile techniques available for the examination and analysis of the microstructure and morphology. Commonly, dried biosorbents must be mounted on special holders using a conductive carbon double-sided sticky tape. To increase image contrast and to avoid undesirable charging effects, it is necessary to coat the sample with a thin layer of a high electrical and thermal conductivity material such as gold, platinum, or carbon. Studies reporting the utilization of the SEM analysis for comparing the surface of biosorbents before and after aflatoxin adsorption are still meager . In the n et al.  showed taccuracy .Pyracantha leaves showed a distinctive amorphous structure based on broad diffraction peaks . Although reduction in crystallinity leads to more reactive samples (X-ray diffraction (XRD) is another non-destructive characterization technique suitable to study phase, structure, orientation, and other structural features such as crystallite size, unit cell dimensions, crystallinity, and crystal defects. In this technique, diffraction patterns are formed by constructive interference of a monochromatic beam of X-rays scattered at different angles. In the analyzed samples, amorphous regions generate broad peaks, whereas crystalline regions produce sharp peaks. In general, X-ray diffractograms are collected using CuKα radiation (λ = 0.15406 nm) over the 2θ range (10 to 100 degrees) with a fixed power source. The XRD patterns of biosorbents are rarely presented in the literature due to the fact that most of the biomaterials used for mycotoxin adsorption are essentially carbonaceous. However, the XRD patterns for banana peel and on peaks . Both bi samples , the adsin vitro, in vivo, and in silico methodologies have been applied to evaluate the potential of these biosorbents in removing or reducing the impact of aflatoxins. A number of factors influencing the adsorption such as physical or chemical modification of the biomaterials, particle size, contact time, pH, temperature, biosorbent dosage, and the aflatoxin concentration, were further reviewed. We found the following:Aflatoxins are inevitable contaminants of food and feed. Because of the adverse effects of aflatoxins on human and animal health, effective, practical, and inexpensive decontamination protocols are highly desirable. Recently, biosorption has received extensive attention among scientists for aflatoxin decontamination due to the low cost and the extraordinary efficiency of the biosorbents. Byproducts such as grape and olive , banana peel, Formosa firethorn (leaves and berries), lignins, micronized fibers, durian peel, seaweeds, Aloe vera powder, lettuce, kale, and field horsetail have received particular attention for the removal of aflatoxins owing their abundance worldwide. As a result, several Structural changes following physical or chemical modifications of the biosorbents may explain their higher efficiencies in adsorbing aflatoxins.Biosorbents with large particles yielded lower adsorption uptakes. However, aflatoxin adsorption significantly increased by decreasing particle size.Generally, the rate of aflatoxin adsorption was accomplished in a short period of time (from 3 up to 30 min). This fast kinetic is highly desirable for practical and commercial applications.Various kinds of biosorbents have good efficiencies in adsorbing aflatoxins at acid pHs and were also capable of retaining most of the toxins when pH increases to 7, although some exceptions were observed.in vivo trials.The biosorbents were efficient at temperatures between 37 and 40°C, which is indicative of their ability to adsorb aflatoxins when using Further increments in the amount of biosorbents improve the uptake of aflatoxins due to the existence of more adsorption sites.Some biosorbents exhibited higher percentages of aflatoxin removal at lower toxin concentrations and considerable uptake capacities at higher aflatoxin concentrations .in vitro digestion procedures simulating the environment in the gastrointestinal tract, the tested biosorbents showed low removal efficiencies toward aflatoxins.Generally, when using in vivo trials, some biosorbents counteracted the harmful effects of AFB1, but these were used at higher inclusion levels (up to 8% w/w).In Several characterization techniques such as FTIR, UV-Vis DRS, ζ-potential, pHzpc, SEM, EDS, and XRD have been successfully used to explain the possible mechanisms involved in the biosorption of aflatoxins.Despite the effectiveness of the biosorbents for the decontamination of aflatoxins, future research should be concentrated on the following topics:The effectiveness of biosorbents for removing aflatoxins needs to be extensively studied using dynamic models that simulate the conditions in the gastrointestinal tract on ways of minimizing the use of experimental animals.in vitro) at low inclusion levels  and challenged with more realistic levels of aflatoxins to make these materials very competitive in the commercial sorbent market.Biosorbents can be tested .Agro-waste-based sorbents such as cereal fibers as well as pulp and peels of some fruits may contain mycotoxins; consequently, these biomaterials need to be further analyzed before using them as mycotoxin binders.Novel approaches for the preparation of biosorbents from other agricultural wastes or byproducts are highly encouraged.Finally, in screening for new biosorbents, larger amounts of hydroxyl and carboxyl groups, high number of hydrophobic groups, higher amounts of pigments (chlorophylls), higher negative surface charge, lower pHpzc values, porous microstructure, and larger surface area seem to be the most important particularities to predict the ability of agro-waste-based materials to bind aflatoxins.Considerations on these topics would help advance the search for near-term future commercial applications of unconventional, eco-friendly, and efficient aflatoxin binders of natural origin.AV-D and AM-A: conceptualization. MN-R: investigation. AV-D: data curation. AM-A: writing—original draft preparation. AV-D and GT-I: writing—review and editing. All authors have read and agreed to the published version of the manuscript.This research was funded by UNAM-PAPIIT grant number IN207920.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


This study aims to summarize the clinical and imaging features of cerebral vascular fenestration and to explore the association between cerebral vascular fenestration and cerebral infarction and aneurysm.The computed tomography angiography (CTA), magnetic resonance angiography (MRA), and digital subtraction angiography (DSA) imaging data of 76 cases of cerebral vascular fenestration from January 2021 and December 2021 in the Yantai Yuhuangding Hospital Affiliated to Qingdao University were analyzed. The general information was described. The location, morphology, and size of cerebral vascular fenestration were described. The association between cerebral vascular fenestration and infarction and aneurysm was analyzed.Among 76 patients, a total of 80 fenestrations were detected (two patients had three fenestrations), and basilar artery fenestration was the most common (28/80). The fenestration <5 mm was 43/80, 5–10 mm was 12/80, and ≥10 mm was 25/80. Moreover, 19 patients had other vascular diseases: 10 with aneurysms, 5 with moyamoya diseases, and 4 with cerebral artery dissections. Except for one aneurysm at the site of the fenestration, other aneurysms were separate from the fenestrations. In addition, 37 patients had cerebral infarctions, of which 16 had cerebral infarctions in the blood supply area of the arterial fenestration. Among these 16 patients, there was more cerebral infarction in posterior circulation than in anterior circulation. However, no statistically significant differences were detected in the risk factors between the fenestration-relevant cerebral infarctions group and the non-fenestration-relevant cerebral infarctions group.In our study, cerebral vascular fenestration occurred most frequently in the basilar artery and may be combined with other vascular diseases. Fenestration in posterior circulation may be related to cerebrovascular diseases. Nonetheless, no clear clinical relevance was observed between fenestration and cerebral infarction. Also, we did not find a definite association between fenestration and aneurysm. For fenestration patients with cerebral infarctions, long-term antiplatelet and statin therapy may be safe and effective. Fenestration of the intracranial artery is segmental duplications of the lumen into two distinct channels, each comprising endothelial and muscular layers with or without a shared adventitia . FenestrThe fenestrations of the cerebral arteries appear in all the branches but are most commonly reported in the vertebrobasilar artery , ACA 9)9), MCA –12, ACOAThe study was performed according to the guidelines from the Helsinki Declaration and was approved by the Institutional Review Board of the Hospital. All patients or their legally authorized guardians provided informed consent according to the requirements of the Ethics Committee. Herein, patients whose image findings were compatible with cerebral vascular fenestration in our hospital from January–December 2021 were analyzed in this retrospective study.All the patients underwent DSA or MRA or CTA in our hospital to confirm the diagnosis of cerebral vascular fenestration. The location, morphology, and size of cerebral vascular fenestration were described. Based on the length of the fenestrated vessel branch, fenestration is divided into three types and based on the morphology, fenestration is divided into four variants. According to the correlation between BA and the location of the origin of the anterior inferior cerebellar artery (AICA), BA fenestrations were divided into four types, namely, type I, the fenestration is located proximal to the AICA or absence of AICA; type II, bilateral AICAs symmetrically originating from the fenestrated trunks; type III, a unilateral AICA originating from one side of the fenestrated trunk; and type IV, the fenestration is located distal to the AICA . All 37 The 37 cerebral vascular fenestration patients with cerebral infarction received the dual antiplatelet and lipid regulation treatment during hospitalization (about 7 days). This treatment was continued 3 months after discharge . A routine follow-up was conducted for 1 year through outpatient monitoring or direct telephonic contact with the patients or their relatives.P < 0.05 were deemed statistically significant.All statistical analyses were performed using a commercial statistical software package . Continuous variables were expressed as mean ± standard deviation (SD). Mann–Whitney U-test was used to analyze the difference in age between the fenestration-relevant cerebral infarctions group and the non-fenestration-relevant cerebral infarctions group. Fisher's precision probability test was performed in between-group comparisons of risk factors, including sex, history of stroke, hypertension, diabetes mellitus, dyslipidemia, atrial fibrillation, cerebral artery stenosis, hyperhomocysteinemia, coronary atherosclerotic heart disease, and recurrence of cerebral infarction. Differences with From January 2021 to December 2021, 76 patients with cerebral vascular fenestration were included, including 44 (57.9%) men and 32 (42.1%) women. The age of the cohort ranged from 24–79 (53.9 ± 28.6) years old. Among these patients, 37 had cerebral infarctions, 10 had aneurysms, 5 presented moyamoya disease, and 4 had cerebral artery dissection. All baseline characteristics are shown in P = 0.716), history of stroke , hypertension , diabetes mellitus , dyslipidemia , atrial fibrillation , cerebral artery stenosis , hyperhomocysteinemia , coronary atherosclerotic heart disease , and recurrence of cerebral infarction  between the two groups. Mann–Whitney U test did not detect any difference in age (P = 0.177) between the two groups. We also found that patients with an ischemic stroke focus more on the posterior circulation (87.5%) than on the anterior circulation (12.5%) in the fenestration-relevant cerebral infarction group. In addition, among the patients with fenestration in the anterior circulation fenestration, 54.2% of patients were <60 years old and 45.8% of patients were >60 years old, and among the patients with fenestration in the posterior circulation, 49.1% of patients were <60 years old and 50.9% of patients were >60 years old; hence, there seems to be no obvious age difference. After dual antiplatelet and lipid regulation therapy, no acute stroke or TIA occurred, while there were no adverse events emerged in 37 fenestration patients with cerebral infarctions during the follow-up.The 37 fenestration patients with cerebral infarction were divided into two groups. Among them, 16 patients with cerebral infarctions in the blood supply area of the arterial fenestration comprised the fenestration-relevant cerebral infarctions group. The remaining 21 patients were assigned to the non-fenestration-relevant cerebral infarctions group. The risk factors of cerebral vascular fenestration patients with cerebral infarctions were compared between the two groups . Fisher'A total of 80 fenestrations were detected in 76 patients. BA fenestrations accounted for 35% (28/80) of all fenestrations. The BA fenestrations were classified as follows: type I, 9 cases; type II, 9 cases; type III, 5 cases (of which one case had only one anterior inferior cerebellar artery and originated from the fenestration); and type IV, 5 cases. Moreover, among the other types of fenestrations, vertebral artery (VA) fenestration accounted for 30% (24/80), anterior communicating artery (ACOA) fenestration accounted for 11.25% (9/80), middle cerebral artery (MCA) fenestration accounted for 8.75% (7/80), anterior cerebral artery (ACA) fenestration accounted for 8.75% (7/80), internal carotid artery (ICA) fenestration accounted for 3.75% (3/80), and posterior inferior cerebellar artery (PICA) fenestration accounted for 2.5% (2/80) of all fenestrations. Among these fenestrations, 25 had a slit-like configuration , 2A,B, wThe results showed that most of these patients with fenestration are accompanied by other diseases: 37 patients had cerebral infarctions; 16 patients had cerebral infarctions in the blood supply area of the arterial fenestration; 10 patients had aneurysms, where only one aneurysm was detected at the site of fenestration; 4 patients had artery dissection, and 2 dissections were at the site of fenestrations; and 5 patients had moyamoya disease, and all “Smog-like” vessels were distal from fenestration.In addition, special cases were detected among these patients. The first case presented triple fenestrations of the anterior communicating artery . The secThe fenestration will cause hemodynamic changes in the vessels in which it is located, and whether it will cause the occurrence of other diseases is still unknown. Therefore, in the present study, we aimed to analyze the characteristics of cerebral artery fenestrations and explore the clinical relevance between cerebral vascular fenestration and cerebral infarction and aneurysm. The results showed that no clear clinical relevance was observed between fenestration and cerebral infarction, and no definite association was found between fenestration and aneurysm. Furthermore, we also found that fenestration in the posterior circulation may be related to cerebrovascular diseases.Some studies have reported that cerebral artery fenestration is associated with cerebral ischemia or TIA , 15–18, Previous studies have described the connection between the fenestration of the intracranial artery and cerebral aneurysm –23, whilIn addition, 4 patients with cerebral artery dissection were found. Among them, 2 dissections were located at the site of fenestrations, and 2 dissections were different from fenestration. The clinical relevance between cerebral artery dissection and fenestration has not been reported previously. Although fenestration alters vascular hemodynamics, whether this will lead to dissection still needs to be investigated further.In our study, we also found that the ischemia focus of the 16 patients was located in the territories of fenestrated arteries, including 12.5% (2/16) in the anterior circulation and 87.5% (14/16) in the posterior circulation, which is similar to the finding of Ye et al. , indicatNevertheless, the present study has some limitations. First, it was a retrospective study with a small sample size. Second, most patients had different degrees of cerebrovascular stenosis, which increases the incidence of cerebral infarction. Finally, since the radiologists were not explicitly looking for fenestrations when they read the images, it is possible that many patients were not included in this study. Hence, a multicenter study with a large number of patients would provide definite data about the location, morphology, and configuration of cerebral artery fenestrations.In the current study, basilar artery fenestration is the most common form of the condition. Fenestration can be divided into four variants, namely, slit-like shape, convex lens-like shape, duplicated artery, and other irregular shape fenestrations. The most common types were slit- and convex lens-like shapes. In this retrospective study, we did not observe a clear clinical relevance between fenestration and cerebral infarction. Also, we did not find a definite association between fenestration and aneurysm. Interestingly, fenestration in the posterior circulation may be related to cerebrovascular diseases. Furthermore, for those fenestration patients with cerebral infarctions, the long-term antiplatelet and lipid-lowering treatment may be safe and effective. Finally, a large multicenter study could be used to explore the clinical relevance between cerebral artery fenestration and other associated vascular diseases.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.The studies involving human participants were reviewed and approved by the Institutional Review Board of Yantai Yuhuangding Hospital. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.ZL, LX, and XC contributed to the study concept and design, data analysis, interpretation, and also guarantors of this work and have full access to the data. LX and XC managed the literature search and analysis. LX undertook the statistical analysis and wrote the first draft of the manuscript. HW, XC, and WX collected and analyzed the data. All authors contributed to the article and approved the submitted version.


Due to the heterogeneous nature of type 2 diabetes mellitus and its complex effects on hemodynamics, there is a need to identify new candidate markers which are involved in the development of type 2 diabetes mellitus (DM) and can serve as potential targets. As the global diabetes prevalence in 2019 was estimated as 9.3% (463 million people), rising to 10.2% (578 million) by 2030 and 10.9% (700 million) by 2045, the need to limit this rapid prevalence is of concern. The study aims to identify the possible biomarkers of type 2 diabetes mellitus with the help of the system biology approach using R programming.MCL1, PTX3, CYP3A4, PTGS1, SSTR2, SERPINA3, TDO2, and GALNT7.Several target proteins that were found to be associated with the source genes were further curated for their role in type 2 diabetes mellitus. The differential expression analysis provided 50 differentially expressed genes by pairwise comparison between the biologically comparable groups out of which eight differentially expressed genes were short-listed. These DEGs were as follows: The cluster analysis showed clear differences between the control and treated groups. The functional relationship of the signature genes showed a protein–protein interaction network with the target protein. Moreover, several transcriptional factors such as DBX2, HOXB7, POU3F4, MSX2, EBF1, and E4F1 showed association with these identified differentially expressed genes.The study highlighted the important markers for diabetes mellitus that have shown interaction with other proteins having a role in the progression of diabetes mellitus that can serve as new targets in the management of DM. Type 2 diabetes mellitus is known to be a life-long disease that is linked to disturbances in glucose levels in the blood. This disease acts as a silent killer that is affecting a wider population of the world. The need to develop potential target hypoglycemic agents as well as new biological candidates and possible treatment strategies has been emphasized in order to combat this disease . Type 2 In-silico or docking studies are those research tools that are “run on or performed on a computer or done via computer simulation.” Drug designing and discovery involves the development of new potential targets for drug molecules through computer simulation, and it is a rapidly emerging trend nowadays . All the cDNA datasets included various information including platform, GEO accession number, number of samples, sample type, and genetic expression data. The differentially expressed genes were identified using the array platform and the annotation platform hgu133plus2 probes. For the computational analysis, the R programming and the Bioconductor packages, affy QC Report, affy, annotate, AnnotationDbi, limma, Biobase, AffyRNAdegradation, hgu133plus2cdf, and hgu133a2cdf, were used .The phenodata files for each dataset having the “.cel format” were prepared for initial preprocessing. For normalization, the Bioconductor Array Quality Metrics package was employed in R programming to a median expression level for each gene (version 3.1.3). After the normalization, the second step was the background correction for perfect match (pm) and mismatch (mm) using the robust multiarray analysis (RMA). This method reduces the local noise present in the background. Afterward, the RMA algorithm summarization was performed to measure the averages among the probes in a probe set and to attain the summary of intensities.p-values that were then ranked. The cutoff values for shortlisting the genes were p-value ≤0.05, false discovery rate (FDR)  <0.05, and absolute log fold change logFC  >1 , Medical Subject Headings (MeSH) (http://www.ncbi.nlm.nih.gov/mesh), Online Mendelian Inheritance in Man (OMIM) (http://www.ncbi.nlm.nih.gov/omim), and PubMed Central (PMC) databases (http://www.ncbi.nlm.nih.gov/pmc). Biomedical text mining was done to filter the potential genes specific to the disease.The differentially expressed genes obtained after shortlisting were further mapped to confirm their role in type 2 diabetes mellitus. This was done with the help of varied data sources such as PubMed  and the Human Annotated and Predicted Protein Interaction (HAPPI) databases helped in evaluating the interaction of proteins with each other having a confidence score of 0.999. The Cytoscape software  was utilized to visualize and analyze the molecular interactions of signature genes with the target genes. Various databases including OMIM, MeSH, and PMC were used to recognize the role of target genes in type 2 diabetes mellitus, and the associated gene signatures cause a pathological phenotype by dysregulation. The online tool Database for Annotation Visualization and Integrated Discovery (DAVID) and the functional enrichment tool FunRich were used to study the physiological functions of signature genes including functional annotation and gene ontology .www.mirdb.org). It is an online database for the target prediction and functional annotation of miRNAs. The target score (≤99) was used to select miRNAs.miRNAs have shown a potential influence on gene targets, and hence, the prediction of miRNAs has proven beneficial in better understanding disease etiology. Several diseases are linked to the dysregulation of miRNAs causing disruption of signaling pathways. Therefore, RNA prediction was done using the miRDB target predictor  and one was downregulated (CYP3A4). The cluster analysis was done by using the CIMminer tool that showed variations between the control and treated groups using yellow and blue colors.In this study, the affy package was implemented in the R statistical program and scripting language for several reasons . The sofMCL1 belongs to the BCL2 family of antiapoptotic proteins, that is, myeloid cell leukemia sequence 1 (Mcl-1). It is an apoptosis regulator and type 2 diabetes mellitus is triggered by impaired β-cell function. The pro-inflammatory cytokines downregulated the MCL1 gene causing β-cell apoptosis  and also the non-diabetes-associated proteins (colored in yellow). Several interacting proteins that showed association with mellitus , 30, 31.mellitus . Most ofMCL1, PTX3, CYP3A4, PTGS1, SSTR2, SERPINA3, TDO2, and GALNT7 were the identified DEGs. Several lines of evidence have shown the role of these genes in the development of diabetes mellitus. Moreover, the study has also explored the interaction of these genes with other proteins involved in crosstalks with these genes. The crosstalks between these genes are responsible for the progression and the complications associated with diabetes mellitus. The gene ontology and functional annotation analysis have also helped us in understanding the biological processes, pathways, and transcriptional factors associated with these genes. The study has opened new insights related to the role of these DEGs in diabetes mellitus, and targeting these genes could potentially help us in the better management of this disease.The study has helped us in identifying candidate biomarker genes for diabetes mellitus using differential expression analysis. The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Conceptualization: TH, UI, RA, and MA. Writing—original draft preparation: BN, UI, RA, and MA. Writing—review and editing: BZ, HZ, AP-S, NN, and MI. Supervision: UI, MA, and YD. All authors have read and agreed to the published version of the manuscript.This study was financed by Riphah International University (Riphah-ORIC-21-22/FPS-51 and Riphah-ORIC-21-22/FPS-56).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interestAll claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Forty-nine sequences (58.3%) were classified as subtype B, followed by C (14.3%), D, and F1 (2.4% each). A complex and dynamic HIV-1 epidemic is observed in the prisons, as 25% of the sequences were recombinant forms. We detected 15 HIV transmission clusters composed of at least two sequences, that included not only prisoners but also individuals from the general population from the same State with a variety of risk behaviors. Thirty-two percent (32.0%) of treatment-experienced prisoners had at least one drug resistance mutation (DRM), while transmitted DRMs were found in 5.9% of the prisoners. We highlight the urgent need for routine surveillance of HIV-1 infection including resistance genotypic tests considering the high disease burden, risky behaviors inside prisons, and the dynamic relationship of prisoners with the outside community.Higher rates of human immunodeficiency virus (HIV) infection have been detected in prisoners when compared with the general population, but research into HIV molecular epidemiology and its transmission network has been lacking among them. Thus, this study aimed to verify potential HIV molecular transmission networks among prisoners. In addition, we aimed to describe the mutations related to antiretroviral resistance in these isolates. Thus, we conducted a cross-sectional survey from 2013 to 2018 in prisons in Central-Western Brazil, and the final sampling composed of 84 prisoners. Proviral DNA was extracted from each whole blood sample followed by amplification of the partial  The prison population has increased by 175% in South America between the years 2000 and 2020 , thus deIn Brazil, screening for human immunodeficiency virus (HIV) infection may be recommended for prisoners who present high-risk behaviors. Counselling, treatment, and care should be part of an HIV program aimed at improving health care in prison and at making it correspond to that offered to the public . CurrentOnce diagnosed, HIV infection should be treated using antiretrovirals (ARV), which are freely available to all HIV-infected persons in Brazil, as well as to prisoners, in the public health system. However, the prisoners usually present low adherence to treatment leading to virologic failure, as demonstrated previously ,7, whichHIV infection is almost ten times more prevalent in prison than in community settings . As therAs the prevalence of HIV infection is higher in prisons, this high rate may reverberate throughout the community because prisoners have regular sexual intercourse with their partners living outside the prison  . In addiOne way to investigate the existence of HIV transmission networks is to use phylogenetic analysis. Phylogenetic and phylodynamic approaches are broadly used to update HIV epidemiology, infer changing trends in the local and regional spread of HIV-1, and guide prevention measures and public health interventions ,22,23. TWe conducted a cross-sectional survey, using information from databases, samples from biorepository, and active searching, with the completion of laboratory analyses. This study was conducted among prison inmates from 2013 to 2018. Whole blood samples were collected in two previous cross-sectional studies ,24 and aInclusion criteria were: (a) a confirmed diagnosis for HIV-1; (b) being a prisoner over 18 years old; (c) having signed the informed consent form in earlier surveys, which predicted storage of samples and their utilization in future research; (d) having sample stored in sufficient quantity to perform the analyses proposed and (e) quality of samples for sequencing. Duplicated samples and those that resulted in poor quality of sequencing were excluded, as depicted in the flowchart .This study was approved by the Ethical Committee on Human Research of the Federal University of Mato Grosso do Sul in 2018 , which is in accordance with the Declaration of Helsinki.polymerase (pol) gene including the protease/reverse transcriptase (PR/RT) region was amplified by nested polymerase chain reaction (PCR) using the combinations of primers previously described  Version 6.0 , which up-value of 0.20 or less were included in the logistic regression backward stepwise model. A p-value of < 0.05 was defined as statistically significant. Odds ratios and 95% confidence intervals (CI) were used as the measure of the strength of the association between outcome and independent variables.Statistical analysis was conducted using the STATA 13.0 software . Median, standard deviation (SD), range, and frequencies (%) were used to describe patients’ characteristics. The frequency of DRMs was also calculated, and the chi-square test or Fisher’s exact test was employed when appropriate. Variables with a The mean age of the 84 studied subjects was 35.8 years (SD 9.27), ranging from 19 to 56 years. As the prison population is composed mainly of men, 76 individuals were male (90.5%) and only 8 (9.5%) were female. Concerning individual original residence, 64% of them were from the Midwest region, however, 59.5% of the individuals were born in another Brazilian state, but were detained in prisons in MS. More than half of the participants were non-white (63.0%), heterosexual (83.3%), and reported a low level of formal education .A total of 102 subjects were recruited, proviral DNA was extracted from whole blood samples of 100 individuals for whom we had biological material stored, and partial polymerase fragment was amplified by nested-PCR in 93 of them. Seven samples were excluded for being double sampled and two due to poor sequencing quality. Therefore, molecular results from 84 sequences were available for the following analysis . Phylogep = 0.01), and being infected by a non-HIV-1B subtype is a protective factor for clustering  of the sequences were found to be linked to at least one another sequence grouped into 17 distinct clusters . After tustering , howeverAmong HIV-1 subtype B samples, 17 of 49 sequences isolated (32.7%) were involved in clusters. These clusters were formed by prisoners’ sequences and other studies from MS available in Los Alamos Sequence Database and obtained previously by these studies conducted among different population groups such as patients from reference centers for HIV-1 treatment, men who have sex with men (MSM), and prisoners ,37,38. MSix clusters  contained two sequences each. Three of them contained a male prisoner and a female from the community , from the remaining three, one was male-only and two of them were formed by a prisoner and a male from the community (clusters 8 and 16) and another one, was formed by two prisoners from the same penal institution (cluster 15). Interestingly, no sequences from the other Brazilian States were clustered together with MS’ sequences of HIV-1B.Only one cluster composed by two study samples  and two others sequences obtained from Los Alamos sequence database was formed in the HIV-1 subtype C analysis. Of these, one was an MSM from MS and the other is a sequence collected in 2006 in Rio de Janeiro state, whose epidemiological data is lacking.Regarding antiretroviral treatment, most  of individuals were treatment-experienced, while 40.5% (34/84) were ART-naïve. Resistance analysis of PR and RT sequences from the 50 ART-experienced samples showed an alarming prevalence of ADRM, since 16/50 (32.0%) of them had at least one DRM. The distribution of resistance mutations by drug-class reflected the predominance of non-nucleoside reverse transcriptase inhibitors , followed by nucleoside reverse transcriptase inhibitors , and protease inhibitors . Of these, eleven were singleton mutations, and five, multiple. The most DRM detected was K103N to NNRTI (9/15). Meanwhile, TDRM were detected in 2/34 (5.9%) ART-naïve samples, one of them presented only K103N, and another accumulated three mutations, K219Q, K103N, and L90M .Particularly in developing countries, prisons have been known as hotspots of several pathogens, including HIV-1, as a result of overcrowding, insufficient health assistance, and prisoners’ high-risk behaviors ,39. ConsTo our knowledge, there is a single study evaluating HIV infection features in the prison population from Central-West Brazil . It was p = 0.002) [Considering the data published so far, relevant data on the molecular epidemiology of HIV-1 in Brazilian prisons are scarce, thus limiting comparisons. In our sampling, HIV-1 subtype B was the most prevalent . This finding is consistent with studies in the general population from the same region, ranging from 65.3 to 69.9% ,41,42, aFor HIV-1, genetic diversity accumulates rapidly, making it conceivable to infer the viral transmission network using phylogenetic reconstruction. Hence, it is possible to describe feasibly the history of infections of these closely related viruses in a phylogenetic tree, assuming that the hosts are connected by a common source, a direct or a short chain of transmissions, especially when detailed epidemiological data is available . In thisOne of the clusters (cluster 15) involved two individuals imprisoned in the same prison facility, suggesting an epidemiological link between them. In addition, we described clusters involving individuals with different HIV risk behaviors, such as MSM and prisoners , and others with no commonly identifiable type of exposure. This supports the idea that the HIV-1 variants circulating in the prison environment may influence the maintenance of their circulation and dissemination in the community. Thus, preventive measures, better opportunities for diagnosis, and adequate treatment of prisoners with HIV can have effects not only on the quality of life and survival of these individuals but also on the community.The present study for the first time investigates the transmission networks in prisoners from MS State and verified the increased possibility to be involved in a cluster when belonging to subtype C and having homosexual contact. Since subtype C prevalence in MS is 14.3% in the present study and 8% in our previous study , the forThe high prevalence of individuals who were not on antiretroviral treatment at the time of blood and data collection (40.5% ART-naïve) also demonstrates that opportunities for diagnosis and treatment are being missed, a reflection of the failure of health policies in Brazilian prisons. Furthermore, a previous study in the same prison facilities showed that, for inmates with a confirmed diagnosis of HIV-1 infection for whom free treatment is offered, approximately half of them presented viral load > 200 copies/mL [Regarding ADRM, 32.0% of treatment-experienced prisoners had at least one DRM, thus pointing out poor treatment adherence, which is common among high-risk behavior groups. TRDM were found in 5.9% of the prisoners, in a setting where pre-treatment genotyping is not a routine, as the Brazilian Ministry of Health recommends it only in specific cases. A study conducted in southern Brazil showed 24% of transmitted and acquired resistance mutations to antiretroviral drugs and an alarming proportion of virologic failure in prisoners on antiretroviral treatment .The mutation K103N was found in 11 prisoners (13.1%), 9 as an ADRM and 2 as a TDRM. This substitution may cause high-level reductions in nevirapine and efavirenz susceptibility. These drugs are not part of first-line antiretroviral treatment in Brazil for all person living with HIV/aids. However, it becomes a concern since efavirenz is part of the preferred regimen  in the treatment of individuals coinfected with tuberculosis (TB) . TB is hThis study has some limitations. We interviewed all individuals face-to-face; consequently, risk behaviors may have been under-reported, leading to potential underestimation of associations with these variables and DRM prevalence. This research comprises not only individuals with epidemiological features in common but also the spread of strains between different key populations, like MSM and prisoners. We highlight that HIV-1 may be circulating not only behind the bars but also in the community outside them. So, it can help to understand that public health interventions in different scenarios, like prisons, may affect the whole epidemic.We acknowledge that our sample size and sampling are not representative of the entire prison population in Brazil. However, the remarkable HIV-1 genetic diversity, the diverse recombination patterns, the high rate of acquired resistance, and the possible transmission links among prisoners and individuals from the general population described in this study raise important public health concerns. Moreover, our data highlight the need for routine surveillance of HIV-1 infection including resistance genotypic tests for prisoners by public health institutions. Considering the high disease burden and risk behaviors inside prisons and the dynamic relationship of prisoners with the outside community, great benefits could be achieved from specific programs aimed at STI, especially HIV prevention, counseling screening, and treatment.


Recently, various hemocyte and blood cell ratios have garnered researchers' attention, as a low-cost, widely prevalent, and easy-to-measure index for diagnosing and predicting disease. Therefore, we sought to investigate the effect and predictive value of the peripheral blood neutrophil percentage and neutrophil-lymphocyte ratio (NLR) in the acute phase of ischemic stroke (AIS) in post-stroke cognitive impairment (PSCI).We selected 454 patients with mild AIS and acquired general clinical data. The patients were divided into PSCI and post-stroke no cognitive impairment (PSNCI) groups according to their Montreal Cognitive Assessment (MOCA) scores. We assessed whether there were differences in clinical data, peripheral blood neutrophil percentage, and NLR values between the different groups. We also analyzed the independent influences on the occurrence of PSCI using a binary logistic regression. Receiver operating characteristic (ROC) curves were used to analyze the predictive value of the above inflammatory indicators and models containing different inflammatory indicators for PSCI.In total, 454 patients were included, of whom 253 (55.7%) patients were in the PSCI group, with a mean age of 62.15 ± 7.34 years and median neutrophil percentage and NLR of 0.64 (0.32–0.95) and 2.39 (0.71–54.46), respectively. Both neutrophil percentage  and NLR as a categorical variable  were independent risk factors for PSCI, and the Q5 group (NLR ≥ 4.05) had significantly worse overall cognition and executive function.Neutrophil percentage and NLR in the acute phase of AIS were independently associated with PSCI, and a high NLR was strongly associated with executive function. In addition, neutrophil percentage and NLR have diagnostic values for PSCI. Post-stroke cognitive impairment (PSCI) is a clinical syndrome characterized by cognitive impairment beginning post-stroke and lasting until 6 months. It occurs in approximately one-third of stroke patients . AlthougThe exact pathophysiological mechanisms underpinning PSCI remain unclear. It is currently believed that the triad of hypoperfusion, oxidative stress, and inflammation, acting alone or in combination, affects the neurovascular unit and is thus involved in the pathogenesis of vascular cognitive impairment. Inflammation and immune response are involved in the pathogenesis of AIS , 3. PrioIn total, 454 patients with mild AIS who had been admitted to the Department of Neurology at the First Hospital of Jilin University between April 2019 and October 2021 were selected. The flow diagram of the study is demonstrated in We acquired general clinical data during hospitalization, including age, sex, education level, body mass index (BMI), and systolic and diastolic blood pressure measured for the first time after admission. The internationally accepted trial of org 10172 in acute stroke treatment (TOAST) typing was used to classify cerebral infarction according to its cause, including large artery atherosclerosis (LAA), cardiogenic embolism (CE), small artery occlusion (SAA), other causes (OD) and unexplained (UD)  and scalRoutine blood samples were acquired within 24 h of AIS occurrence to examine for neutrophil percentage, absolute neutrophil value, and absolute lymphocyte value. Fasting blood glucose, various lipids, uric acid, cystatin C, homocysteine, and CRP were collected on the following day, while NLR was equal to the absolute neutrophil value/absolute lymphocyte value. The study subjects were placed into five groups according to the NLR quintiles: Q1 (≤ 1.62), Q2 (1.63–2.08), Q3 (2.09–2.72), Q4 (2.73–4.04), and Q5 (≥4.05). All blood samples were obtained from the Biobank of the First Hospital of Jilin University. Complete blood count was measured using a SYSMEX XN-9000 hematology analyzer  according to the manufacturer's recommendation.The following imaging measures were collected within 72 h of AIS: the diameter of maximum transverse section (DMTS) of the infarct was measured based on brain MRI DWI axial position to assist in the assessment of infarct size in AIS. For the convenience of the analysis, the brain circulation was divided into anterior circulation, including frontal, parietal, lateral temporal cortex and subcortical areas, internal capsule and basal ganglia, and posterior circulation, including brainstem, cerebellum, thalamus, medial temporal lobe, and occipital areas. In addition, to analyze whether the infarct number affected PSCI, we included either a single or two numbers. We also analyzed the effects of white matter loose grade on PSCI, including periventricular hyperintensity (PVH) and deep white matter hyperintensity (DWMH) through imaging. All of the imaging data described above were evaluated by a professional imaging physician.On days 7 to 10 following AIS, when the symptoms of cerebral infarction were relatively stable, cognitive psychological assessments were carried out on all included patients by psychometrically qualified assessors in a relatively quiet environment, without any other patient present at the same time. The overall cognitive function was assessed using the MOCA, with a total score of 30. MOCA is strongly correlated with educational level; studies have revealed that the corrected MOCA score increased by 1 when the length of education is <12 years . Assessmt-test, whereas nonparametric continuous variables  are represented as the median (quartile 25-quartile 75). Groups were compared using a Mann–Whitney U test. Categorical variables  are presented as the number (n) and proportion (%). Groups were compared using a chi-squared test. Univariate and multivariate logistic regression analyses were used to investigate the correlation between percent neutrophils, NLR, and PSCI. Multivariable models were adjusted for variables with a p < 0.1 in the univariate analysis. Univariate included general clinical data , various laboratory indicators, cognitive scores, and imaging data . An association was indicated as the odds ratio or adjusted odds ratio (aOR) with the 95% confidence interval (CI). To evaluate the collinearity among the different peripheral blood inflammation indicators, a regression analysis was carried out to judge the independent influencing factors of PSCI. The ROC curve was used to analyze the predictive value of models containing different inflammatory indicators and single inflammatory indicators for PSCI. All statistical analyses were performed in SPSS version 23 . Statistical significance was defined as a two-sided P-value of < 0.05.Parametric continuous variables  are expressed as the mean (± standard deviation). Groups were compared using an independent Student's A total of 454 patients with mild AIS in the acute phase were included, of whom 253 (55.7%) patients were in the PSCI group, with a mean age of 62.15 ± 7.34 years and median neutrophil percentage and NLR of 0.64 (0.32–0.95) and 2.39 (0.71–54.46), respectively. There were 326 males (71.8%), and their median level of education was 9 (0–19) years. According to TOAST typing, the LAA had the largest proportion of cerebral infarcts (52.2%), followed by the SVO (37.7%). Only 25.8% of patients had infarcts in key memory-related sites such as the thalamus, hippocampus, medial temporal lobe, and angular gyrus; the median DWMH and PVH grades were 2 and 1, respectively. As regards past medical history, the prevalence rates of a positive history of hypertension, diabetes, previous stroke, heart disease, smoking, and drinking were 63.9, 31.1, 26.4, 17, 50.9, and 45.2%, respectively.P < 0.05) (see The PSCI group had a higher proportion of previous hypertension (68.0%) and stroke history (30.8%) than those of the PSNCI group . PSCI occurred more frequently in patients with ≥ 2 infarct foci (50.2%) than in those with single infarct foci (38.3%), with the highest proportion of PSCI occurring in patients with anterior circulation infarction (53.4%), followed by those with posterior circulation infarction (35.2%), and both anterior and posterior circulation (11.5%). Patients in the PSCI group were older, had lower education levels, higher admission systolic blood pressure and overall NIHSS scores, larger DMTS and lower uric acid levels, and more severe DWMH. In addition, the two groups had statistically significant differences in memory, language, and executive and visuospatial areas, with the PSCI group having lower scores across all cognitive domains than that of the PSNCI group (.05) see .P < 0.05); the percentage of neutrophils (0.66) and NLR (2.65) in the PSCI group was higher than that in the PSNCI group , and the other two indicators were lower than that in the PSNCI group.A comparison between the PSCI and PSNCI groups regarding peripheral blood inflammatory markers see  revealedP < 0.05).Considering that NLR, a continuous numerical variable, was statistically different between the two groups of PSCI and PSNCI, we further assessed whether there were differences across the two groups at different NLR levels. As represented in P < 0.05).In summary, the peripheral blood inflammatory index, neutrophil percentage, NLR, and NLR quintile were statistically different between the two groups of PSCI and PSNCI  and in the trend chi-square test. The risk of PSCI increased as NLR increased  than in NLR (<1.62), and 2.167 times higher in NLR (≥4.05) than in NLR (≤1.62)  released by neutrophils at different stages of AIS may be involved in the development of PSCI by causing hypoperfusion, BBB destruction, brain parenchymal damage, and reduced neovascularization, affecting the structural integrity of the neurovascular unit , 20–23. The NLR as a marker of systemic inflammation is more responsive to clinical significance than neutrophils and lymphocytes alone, and it is useful , low cosWe demonstrated that peripheral blood inflammatory indicators in the acute phase of AIS can be used as predictors of the development of PSCI and have diagnostic value, providing a new idea for clinical research related to peripheral immunity and PSCI. Among them, the cognitive assessment in the acute phase of stroke was conducted on days 7–10 after stroke, and during this period, the symptoms of cerebral infarction are relatively stable, which can avoid the interference of cognitive stress damage caused by stroke itself. However, this study has some limitations. First, our data were acquired from a single center. Second, as PSCI could happen right after the stroke and last for 6 months, the follow-up evaluation of the CI is critical, other than 7–10 days post stroke. We also performed cognitive follow-up of some patients at 3 months, 6 months, and 1 year after stroke. Due to the global outbreak of COVID-19 during this period, most patients could not come to the hospital on time to complete the follow-up on time. Therefore, our cognitive follow-up data were insufficient and inconsistent. In future studies, we will refine the analysis at 3 and 6 months after stroke to get a better understanding of the association of peripheral immunization with PSCI. Afterward, we did not collect specific cognitive level and laboratory indicators before stroke. However, we asked about a detailed medical history of the study population, excluding people who were diagnosed with dementia before stroke or who had used drugs affecting cognitive impairment in the 2 weeks before screening, excluding related diseases affecting peripheral blood routine. We hope to design and collect data of patients before stroke in future studies to obtain the higher-quality clinical research result. Finally, the diagnostic accuracy of the peripheral blood index in the acute stroke phase for PSCI was moderate, and further research is expected to explore its real value. Screening patients at high risk of cognitive impairment using acute stroke inflammatory markers combined with history and imaging may enable a future follow-up to be completed 3–6 months following a stroke, with data collected on routine blood and cognitive assessments, to establish a longitudinal cohort study to dynamically observe the potential value of inflammatory markers for the diagnosis of PSCI.In conclusion, neutrophil percentage and NLR in the acute phase of AIS were independently associated with PSCI. In addition, a high NLR was strongly associated with executive function. In conclusion, neutrophil percentage and NLR provide a certain diagnostic value for PSCI, which is of key clinical relevance.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.The studies involving human participants were reviewed and approved by The First Hospital of Jilin University. The patients/participants provided their written informed consent to participate in this study.TS analyzed the literature and wrote the manuscript. YS, CW, ZW, WZ, ML, and YW collected the data and designed the study. BM contributed to manuscript editing. LS provided the framework for the study and reviewed and edited the manuscript. All authors have read and agreed to the final version of the manuscript.This study was funded by the Ministry of Science and Technology's major chronic disease project of China (No. 2018YFC1312301).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Peritoneal metastasis (PM) is not uncommon in patients with gastric cancer(GC), which affects clinical treatment decisions, but the relevant examination measures are not efficiently detected. Our goal was to develop a clinical radiomics nomogram to better predict peritoneal metastases.A total of 3480 patients from 2 centers were divided into 1 training, 1 internal validation, and 1 external validation cohort with clinicopathologically confirmed GC. We recruited 11 clinical factors, including age, sex, smoking status, tumor size, differentiation, Borrmann type, location, clinical T stage, and serum tumor markers (STMs) comprising carbohydrate antigen 19–9 (CA19-9), carbohydrate antigen 72–4 (CA72-4), and carcinoembryonic antigen (CEA), to develop the radiomics nomogram. For clinical predictive feature selection and the establishment of clinical models, statistical methods of analysis of variance (ANOVA), relief and recursive feature elimination (RFE) and logistic regression analysis were used. To develop combined predictive models, tumor diameter, type, and location, clinical T stage and STMs were finally selected. The discriminatory ability of the nomogram to predict PM was evaluated by the area under the receiver operating characteristic curve(AUC), and decision curve analysis (DCA) was conducted to evaluate the clinical usefulness of the nomogram.The AUC of the clinical models was 0.762 in the training cohorts, 0.772 in the internal validation cohort, and 0.758 in the external validation cohort. However, when combined with STMs, the AUC was improved to 0.806, 0.839 and 0.801, respectively. DCA showed that the combined nomogram was of good clinical evaluation value to predict PM in GC.The present study proposed a clinical nomogram with a combination of clinical risk factors and radiomics features that can potentially be applied in the individualized preoperative prediction of PM in GC patients.The online version contains supplementary material available at 10.1186/s12885-023-10537-7. Gastric cancer is a global health problem, with more than 1 million new cases annually. Although the incidence and mortality of gastric cancer have declined globally in recent years, gastric cancer is still the third leading cause of cancer-related deaths . In receNoninvasive biomarkers can predict the presence of cancer at the early stage and monitor tumor dynamics in real time, as well as predict its prognosis, and have been increasingly used in clinical practice. Serum tumor markers(STMs) have been widely used to diagnose certain populations and monitor the dynamic changes in cancer, for example, CEA, CA19-9 and CA72-4 are three indicators for the diagnosis of gastric cancer, and their elevation is closely related to the occurrence, recurrence and metastasis of gastric cancer –8. In adGastric cancer metastasis is the main cause of death in patients with advanced gastric cancer, and the most common sites of metastasis are the liver, peritoneum, lung and bone. At the same time, different sites of metastasis are associated with different survival times, so it is necessary to determine the prognosis of tumor metastasis sites –13. The In this study, we propose a clinical nomogram method for the preoperative prediction of PM in gastric cancer patients, combining clinical risk factors and radiological characteristics, for individualized preoperative prediction of PM in gastric cancer patients.From January 1, 2018, to December 31, 2021, a total of 3481 eligible gastric cancer patients from the Nanfang Hospital(NFHCC) dataset and 1066 gastric cancer patients from the Wuhan Central Hospital(WCHCC) cohort were included in the study. A flow diagram of the development and validation of the screening of eligible GC patients is presented in Fig. The depth of invasion  was evaluated by preoperative contrast-enhanced abdominal CT imaging within 4 weeks before surgery, and the Borrmann type was obtained from preoperative diagnostic gastroscopy. Both were classified according to the 8th AJCC tumor classification. Laboratory analysis of STMs was performed via routine blood tests within one week before surgery. The detected STMs included carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19–9, and CA 72–4. Tumor marker values above these thresholds were considered positive, otherwise, the sample was deemed negative. Peritoneal metastasis was obtained from medical records.Best subset regression was applied to select the most useful predictive factors from the primary dataset. A predictive score was calculated for each patient via a linear combination of selected features that were weighted by their respective coefficients . To provThe calibration of the nomogram was evaluated by the Hosmer–Lemeshow test and displayed in the form of a calibration curve. The accuracy of the predictive ability of the nomogram over time is displayed in the form of an ROC curve, and the discriminatory ability of the nomogram to predict PM in GC is quantitatively expressed by the AUROC. In addition, decision curve analysis (DCA) was conducted to determine the clinical usefulness of the nomogram by quantifying the net benefits at different threshold probabilities.P < 0.05 in the univariate analysis were included in a multivariate logistic regression model, and all statistical tests were two-sided, with statistical significance set at 0.05.Statistical analysis was conducted with SAS 9.4  and R3.6.2 . The R statistical packages “rms”, “survival”, “Hmisc”,“MASS”, and “timeROC” were used to plot the distribution of risk scores and LNM, build a nomogram, and generate calibration, and time-dependent ROC curves, while “rmda”was used to generate the DCA curves. The categorical variables are expressed as the quantity and percentage, and comparisons were made using the chi-square test or Fisher's exact test where appropriate. All candidate predictors with a P > 0.05). In both cohorts, PM was found to be significantly associated with age, tumor diameter, tumor location, type, T stage, CEA CA199 and CA 72–4.The clinical characteristics of GC patients in the primary and validation cohorts are presented in Table Among the eight simplified clinicopathological features, four variables were selected as the best subset of risk factors to develop the prediction model, including tumor diameter, type, location, and T stage Table . The regThe AUC values of the nomogram for the prediction of PM were 0.762 in the training cohort, 0.772 in the internal validation cohort, and 0.758 in the external validation cohort Fig. . The calTo evaluate the additional predictive value of STMs, three STMs, CEA, CA 19–9 and CA 72–4, together with simplified clinicopathological features, were used to develop a PM prediction model. Finally, seven variables were selected as the best subset of risk factors, including, tumor diameter, type, and location, T stage, CEA,CA199 and CA 72–4 (Table The model (Model 2) that incorporated the above predictors was developed and presented as the nomogram Fig. .Fig. 5ThP = 0.998) and validation cohort (P = 0.888)   Fig. B. After 88) Fig. A, valida88) Fig. B and ind01) Fig. C.DCA is a novel strategy for evaluating alternative predictive treatment methods and has advantages over AUROC in clinical value evaluation. The DCA curves for the developed nomogram in the training, internal validation, and external validation cohorts are presented in Fig. In our study, we combined clinical risk factors, radiographic characteristics of primary lesions and radiographic characteristics of peripheral blood to establish a prediction model to predict PM in GC patients before surgery. The results of this study suggest that model II has better predictive efficacy in both the training and validation sets, and DCA demonstrates that this nomogram is very useful for predicting PM in GC patients before surgery.Currrently, the study of PM in GC patients is one of the GC research hotspots and mainly focuses on molecular biology, machine learning and serum markers. However, no standardized and effective PM prediction scheme has been developed because of the individual differences of patients and the particularity of the disease.Sawaki et al. identified TNNI2 as a candidate for specific overexpression of gastric cancer prone to PM. The high expression of TNNI2 was significantly and specifically correlated with PM . It can Some studies proposed a prediction model based on collagen characteristics, and demonstrated that high collagen characteristics were significantly correlated with the risk of PM(P < 0.001), which can be conveniently used to independently predict the risk of PM after radical resection of gastric cancer . Jiang eSerum markers also play an important role in predicting PM in gastric cancer. In a retrospective cohort study of patients with advanced gastric cancer, a high preoperative neutrophil/lymphocyte ratio was associated with the presence of PM during staging laparoscopy . Qin et In our study, the factors we used to establish the prediction nomogram of PM were easily obtained clinically without any invasive procedure or complicated transformation, and with the combined features, the ability of the model to predict PM was improved. Therefore, the model, can be widely used in the clinic. There are limitations of our study. The main limitation is the retrospective nature of the study. Although this study included patients from two different organizations to assess its reproducibility, this research mainly included patients with gastric cancer, and patients in Western countries. therefore, the model's performance in different ethnic groups also needs further evaluation. While the characteristics of conventional clinical and serological markers were analyzed, and through comparison of different models to generate the best model to predict GC patients with PM, the results indicate that further verification is needed.In summary, PM is occult for clinical detection in GC patients, and the combined nomogram is an improved model for PM prediction.Additional file 1.Additional file 2.Additional file 3.


Chinese children are deficient in several essential nutrients due to poor dietary choices. Dairy products are a source of many under-consumed nutrients, but preschool children in China consume dairy products significantly less than the recommended level.n = 676) were selected. The four-day dietary data (including 2 working days and 2 weekends) collected through an online diary with reference to the food atlas were used for analysis and simulation. In scenario 1, individual intake of liquid milk equivalents was substituted at a corresponding volume by soymilk, cow’s milk, or formulated milk powder for preschool children (FMP-PSC). In scenario 2, the amount of cow’s milk or FMP-PSC increased to ensure each child’s dairy intake reached the recommended amount (350 g/day). In both scenarios, the simulated nutrient intakes and nutritional inadequacy or surplus were compared to the survey’s actual baseline data.From the cross-sectional dietary intake survey of infants and young children aged 0–6 years in China (2018–2019), preschool children (age: 3–6 years) (1, vitamin B3, vitamin B12, vitamin C and vitamin D. Moreover, our results suggested that adding FMP-PSC to bring each child’s dairy intake to the recommended amount can bring the intakes of dietary fiber, DHA, calcium, iron, zinc, iodine, vitamin A, vitamin B1, vitamin B3, vitamin B9, vitamin B12, vitamin C and vitamin D more in line with the recommendations when compared with cow’s milk.It was suggested suggested that replacing dairy foods with FMP-PSC at matching volume is better than replacing them with soymilk or cow’s milk to increase the intake of DHA, calcium, iron, zinc, iodine, vitamin A, vitamin BAccurate nutrition information should be provided to the parents of preschool children so as to guide their scientific consumption of dairy products and the usage and addition of fortified dairy products can be encouraged as needed. Preschool children age: 3–6 years) are still undergoing rapid physical, psychological, and behavioral development, which increases their need for several nutrients, such as protein, polyunsaturated fatty acid, calcium, iron, zinc, vitamin A, B vitamins, vitamin C, and vitamin D , 2. Addi–6 years Although the status of child undernutrition in China has substantially improved due to economic growth, the problem of inadequacy or lack of dietary micronutrients has become prominent. According to China’s national dietary survey, children’s dietary mineral and vitamin intake remained inadequate in the past decade . Dairy pNutritional fortification is one of the primary measures of nutritional intervention, which plays a role in improving the nutritional status of the population . Dairy pIn order to study the impact of dairy products on the dietary nutrition status of children, Jia x et al. utilized data from the China Health and Nutrition Survey 2015 (2015 CHNS) to perform a simulation study on children aged 3–8 years . The resBased on the data from a cross-sectional dietary intake survey of infants and young children aged 0–6 years in China , this study aims to evaluate the impact of dairy products on the dietary nutritional status of 676 preschool children (age: 3–6 years) through two scenarios. In scenario 1, individual intake of liquid milk equivalents was simulated and substituted with a corresponding volume of soymilk, cow’s milk, or formulated milk powder for preschool children (FMP-PSC). In scenario 2, increasing the amount of cow’s milk or FMP-PSC to bring each child’s dairy intake to the recommended amount (350 g/day) was simulated. We hypothesized that the greatest improvements in nutrients of public health concern for preschool children would be observed when using FMP-PSC to simulate each scenario.The data of DSIYC from 2018 to 2019 were used in the analysis. First, two municipalities and 11 provinces, including Beijing, Shanghai, Guangdong, Sichuan, Yunnan, Fujian, Zhejiang, Jiangsu, Anhui, Hubei, Henan, Hebei, and Liaoning, were selected according to their geographical location, economic conditions, and annual live births. Then, the survey city was selected in accordance with the urban and rural areas of each region. Finally, according to the information provided by the maternal and child health center, preschool children were randomly recruited from each city. Based on the survey, we selected the effective dietary data of 676 preschool children aged 3–6 years, including 224 aged 3–4 years, 226 aged 4–5 years, and 226 aged 5–6 years.The dietary intake of preschool children was assessed through the use of an online diary with reference to the food atlas, which was developed by our research group using three visual reference systems, namely, regularly placed food portions, the two-dimensional background coordinates and common objects known in daily life . A food After the food was converted to the weight in its common state , the total daily intake of each kind of food was summed up. The individual components were recorded in the compound processed food, such as steamed stuffed buns, dumplings, wonton, steamed vermicelli roll, Chinese rice pudding, glutinous rice balls, hamburgers, pizza, and sandwiches. For example, in the chicken burger, bread, chicken, lettuce, and cheese were considered separately. The dairy products consumed were divided into 4 categories: liquid milk, milk powder, yogurt, and other dairy products . The amounts of milk powder, yogurt, and other dairy foods were converted into their liquid milk equivalents in accordance with their protein composition. The total liquid milk equivalents were considered as the total intake of dairy products, and the proportion of preschool children who did not meet the recommended 350 g/day dairy intake in the 2022 balanced dietary pagoda for preschool children  was calc1, vitamin B2, vitamin B3, vitamin B6, vitamin B9, vitamin B12, vitamin C and vitamin D. Adequate intake (AI) was used to assess potassium inadequacy. Inadequate fiber intake was defined as the daily intake of <10 g/1,000 kcal energy. The upper limit of the acceptable macronutrient distribution ranges (AMDR) was applied to calculate the proportion of preschool children who consumed excessive fat.The energy and nutrient contents of each food were determined in accordance with the Chinese Food Composition Table (6th edition) . During In scenario 1, the individual intake of liquid milk equivalents was simulated to be replaced with soymilk (model 1), cow’s milk (model 2), and FMP-PSC (Aptamil) (model 3) at a matching volume. In scenario 2, cow’s milk (model 4) or FMP-PSC (model 5) was added so that each child’s dairy intake reached the recommended amount (350 g/day). In both scenarios, the nutrient intakes and the proportion of children with nutritional inadequacy or surplus after simulation were compared with the actual reported data. Nutritional composition per 100 g of soymilk, cow’s milk, and FMP-PSC used for simulation scenarios were shown in P50 . Categorical variables were expressed as frequency (n) and percentage (%). The participants were grouped by age, and the differences in dairy intake among different age groups were compared by Chi-square test or Kruskal Wallis H test according to the data type. Wilcoxon matched-pairs signed rank test and McNemar paired Chi-square test were applied to compare the differences in the nutrient intake and the changes in the proportion of preschool children with inadequate or excessive nutrient intake before and after modeling, respectively. Kruskal-Wallis H test or Mann-Whitney U test was applied to compare the energy changes of the different models. All data were statistically analyzed using the SPSS software package version 26.0 . The results were considered to be statistically significant at P < 0.05.The normality of the continuous variables was tested and almost all dietary data were determined to show non-normal distribution; accordingly, they were represented by The distribution of dairy intakes before simulation  can be found in Although there was no statistical difference in the proportion of consumers of liquid milk, yogurt, and other dairy products among age groups, there was a statistical difference in milk powder consumption among age groups. Specifically, as children aged, the proportion of milk powder consumed decreased. Although the proportion of children in all age groups who consumed less than the recommended amounts of dairy foods was high and there was no statistically significant difference among the groups, it is worth noting that, the amount of liquid milk equivalent consumed by children per day decreased with age, and the difference among all age groups was statistically significant.In scenario 1, after substituting the intake of liquid milk equivalents with soymilk (model 1), cow’s milk (model 2) and FMP-PSC (model 3) by matching volumes, compared with the reported data, the energy intake of children in all three models was significantly decreased, especially in the replacement of soymilk. The energy changes among the three models showed statistical differences . There wIn scenario 2, after increasing the amount of cow’s milk (model 4) or FMP-PSC (model 5) to make the dairy intake of each child reach the recommended amount, compared to the reported intake, the energy intake of children in both models was significantly increased. The differences in energy between the two models were statistically significant . The chaThe intakes of carbohydrates, protein, fat, dietary fiber, and DHA by different age groups after simulation were shown in In scenario 1, although the calcium intake of children was significantly decreased following the substitution of soymilk (model 1), it was significantly increased after the simulation with cow’s milk (model 2), or FMP-PSC (model 3). Especially in the latter, the proportion of children with inadequate calcium intake decreased from 91.57 to 83.14%. Children’s iron and zinc intake changed similarly following the simulation, and only the replacement of FMP-PSC increased their intake. In addition, no improvement in inadequate iodine and potassium intake was seen as compared to the reported intake .In scenario 2, adding cow’s milk (model 4) or FMP-PSC milk (model 5) significantly increased calcium intake, and the proportion of children with inadequate calcium intake in the total population decreased by 16.13 and 27.22%, respectively. The addition of FMP-PSC significantly increased iron and zinc intake while decreasing the proportion of children with inadequate intake, which was 18.64 and 35.35%, respectively. Similar effects were also found in the addition of cow’s milk, but there was less improvement. The addition of cow’s milk and FMP-PSC both significantly increased children’s intake of iodine and potassium while tend to decrease the proportion of children with inadequate intake .The intakes of calcium, iron, zinc, iodine, and potassium by different age groups after simulation were shown in 1, vitamin B12, vitamin C and vitamin D, while the opposite results were observed following the replacement of soymilk (model 1) or cow’s milk (model 2). The intakes of vitamin B2 and vitamin B6 were decreased following soymilk substitution, while their intakes were slightly increased after simulation with cow’s milk or FMP-PSC. In the models of soymilk and cow’s milk, the improvement of inadequate vitamin B3 intake was limited, but it was improved in the FMP-PSC model. After the simulation, Children’s vitamin B9 intake improved significantly, especially when soymilk was replaced. In the dairy food simulation, FMP-PSC improved on inadequate vitamin B9 intake better than cow’s milk, and the proportion of the total population with inadequate vitamin B9 intake decreased by 1.63 and 13.32%, respectively  increased the intakes of vitamin A, vitamin Bectively .1, vitamin B12, and vitamin C, and decreased the proportion of children with inadequate intakes, which were 33.58, 8.58, 20.41, and 6.95%, respectively. Although the addition of cow’s milk had comparable effects (model 4), there was less improvement. The inadequate intake of vitamin B2 and vitamin B6 was significantly improved, and the effect of adding cow’s milk was greater than that of adding FMP-PSC. The improvement of inadequate intake of vitamin B3 and vitamin D was limited in the model of cow’s milk, but this situation improved in the FMP-PSC model. Furthermore, FMP-PSC improved on inadequate vitamin B9 intake better than cow’s milk, reducing the proportion of children with inadequate vitamin B9 intake by 19.53%  significantly raised the intakes of vitamin A, vitamin By 19.53% .1, vitamin B2, vitamin B3, vitamin B6, vitamin B9, vitamin B12, vitamin C, and vitamin D by different age groups after simulation were shown in Supplementary Table 4 and the changes in these nutrients were similar to those of the whole age group.The intakes of vitamin A, vitamin BThe DSIYC, 2018–2019, on which this simulation study was based, is a cross-sectional survey of Chinese children aged 0–6 years conducted in multiple regions of China from 2018 to 2019. It can be seen from the results that the percentage of consumption and amounts of dairy products consumed have increased in recent years, but the consumption of dairy products by preschool children remains low. According to CHNS 2015, 97.6% of children did not meet the recommended 300 g/day of dairy foods . We founThis study also looked at the trends in dairy consumption among age groups. The results showed that the intake of total dairy products decreased significantly with age, which was consistent with the findings of other studies in China and other countries , 24. How12, and vitamin D than non-consumers , consuming milk was associated with increased calcium, phosphorus, magnesium, potassium, and iodine intakes when compared to those who did not drink milk . Accordionsumers . Data fronsumers . Our stu years, c results . Interesr health , 31.1, vitamin B2, vitamin B3, vitamin B6, vitamin B9, vitamin B12, and vitamin C. Among these micronutrients, except for potassium and vitamin B2, the improvement effect of FMP-PSC on inadequate intakes of micronutrients was significantly better than that of cow’s milk. This result is similar to the previous simulation study based on the dietary survey data of children (1–8 years) in China  is better than replacing with soymilk or cow’s milk in increasing most nutrient intakes in preschool children and adding FMP-PSC to make the intake of dairy products per child reach the recommended amount (scenario 2) can bring the intake of most nutrients of preschool children more in line with the recommendations when compared to cow’s milk. Therefore, to guide the scientific consumption of dairy products, correct nutrition information should be given to parents and preschool children. When necessary, the use and addition of dairy products with food ingredients or nutritional fortifiers can be encouraged. Furthermore, for optimal nutritional intakes of preschool children, in addition to the dietary behavior modification of dairy consumption, a multi-faceted approach that includes a diversified balanced diet and the use of dietary supplements (such as vitamin D) is required.The original contributions presented in this study are included in the article/ZW and YD: conceptualization and design of the work. YD, ZX, GL, YZ, JY, and MF: analysis and interpretation of the work. YD, FH, and GL: writing—original draft preparation. YD, ZX, FH, JY, and ZW: writing—review and editing. ZW: supervision and funding acquisition. All authors contributed to the article and approved the submitted version.