ObjectiveTo explore the material basis of the "interaction of blood stasis and toxin" mechanism in cerebral ischemia-reperfusion injury， as well as the protective role of Huoxue Huayu Jiedu prescription （HXHYJDF） against ferroptosis. MethodsSixty SPF-grade male SD rats were randomly divided into six groups： sham group， model group， deferoxamine （DFO） group （100 mg·kg^-1）， low-dose HXHYJDF group （4.52 g·kg^-1）， medium-dose HXHYJDF group （9.04 g·kg^-1）， and high-dose HXHYJDF group （18.07 g·kg^-1）， with ten rats in each group. Except for the sham group， the other groups were used to replicate the model of focal cerebral ischemia-reperfusion in the middle cerebral artery of rats by the reforming Longa method. Neurological function was assessed at 1^st， 3^rd， 5^th， and 7^th days post-reperfusion using the modified neurological severity scores （m-NSS）. Brain tissue pathology and the morphology of mitochondria were observed using hematoxylin-eosin （HE） staining and transmission electron microscopy. The contents of malondialdehyde （MDA）， glutathione （GSH）， divalent iron ions （Fe²⁺）， and reactive oxygen species （ROS） in the ischemic cerebral tissue were detected using enzyme-linked immunosorbent assay （ELISA）. Immunohistochemistry and Western blot （WB） were used to detect the expression of iron death marker proteins glutathione peroxidase 4 （GPX4）， ferroportin-1 （FPN1）， transferrin receptor protein 1 （TfR1）， and ferritin mitochondrial （FtMt） in brain tissue. ResultsCompared with the sham group， the mNSS score of the model group was significantly increased （P<0.01）. HE staining showed that the number of neurons in the cortex of brain tissue was seriously reduced， and the intercellular space was widened. The nucleus was fragmented， and the cytoplasm was vacuolated. The results of transmission electron microscopy showed that the mitochondria in the cytoplasm contracted and rounded， and the mitochondrial cristae decreased. The matrix was lost and vacuolated， and the density of the mitochondrial bilayer membrane increased. The results of ELISA showed that the content of GSH decreased significantly （P<0.01）， and the contents of MDA， Fe²⁺， and ROS increased significantly （P<0.01）. The results of immunohistochemistry and WB showed that the expression of GPX4 and FPN1 proteins was significantly decreased （P<0.01）， and the expression of FtMt and TfR1 proteins was significantly increased （P<0.01）. Compared with those of the model group， the m-NSS scores of the high-dose and medium-dose HXHYJDF groups began to decrease on the 3^rd and 5^th days， respectively （P<0.05， P<0.01）. The results of HE and transmission electron microscopy showed that the intervention of HXHYJDF improved the pathological changes of neurons and mitochondria. The results of ELISA showed that the content of GSH in the medium-dose and high-dose HXHYJDF groups increased significantly （P<0.01）， and the contents of MDA， Fe²⁺， and ROS decreased significantly （P<0.05， P<0.01）. The content of GSH in the low-dose HXHYJDF group increased significantly （P<0.01）， and the contents of MDA and ROS decreased significantly （P<0.01）. The results of immunohistochemistry showed that the expression of GPX4 and FPN1 in the high-dose HXHYJDF group increased significantly （P<0.01）， and the expression of FtMt and TfR1 decreased significantly （P<0.01）. The expression of GPX4 and FPN1 in the medium-dose HXHYJDF group increased significantly （P<0.05）， and the expression of TfR1 decreased significantly （P<0.01）. WB results showed that the expression levels of FPN1 and GPX4 proteins in the high-dose， medium-dose， and low-dose HXHYJDF groups were significantly up-regulated （P<0.01）， and the expression levels of FtMt and TfR1 proteins were significantly down-regulated （P<0.01）. ConclusionHXHYJDF can significantly improve neurological dysfunction symptoms in rats with cerebral ischemia-reperfusion injury， improve the pathological morphology of the infarcted brain tissue， and protect the brain tissue of rats with cerebral ischemia-reperfusion injury to a certain extent. Neuronal ferroptosis is involved in cerebral ischemia-reperfusion injury， with increased levels of MDA， Fe²⁺， ROS， and TfR1 and decreased levels of FtMt， FPN1， GPX4， and GSH potentially constituting the material basis of the interaction of blood stasis and toxin mechanism in cerebral ischemia-reperfusion injury. HXHYJDF may exert brain-protective effects by regulating iron metabolism-related proteins， promoting the discharge of free iron， reducing brain iron deposition， alleviating oxidative stress， and inhibiting ferroptosis.

The onset of pregnancy is marked by the formation of a zygote, while the culmination of gestation is manifested by the delivery of a fetus. Meanwhile, a successful pregnancy entails a meticulously coordinated sequence of events from embryo implantation to sustained decidualization of the uterus to placental development and childbirth. The decidual reaction, a pivotal process occurring within the endometrium during pregnancy, is finely regulated by sex steroids and cytokines. Notably, fibroblast growth factors (FGFs), particularly FGF2, play a critical role in this physiological cascade. Dysregulated FGF expression may trigger inadequate decidualization, precipitating a spectrum of adverse pregnancy outcomes, including preeclampsia, recurrent implantation failure, and miscarriage. Furthermore, the human decidua, distinct from most mammalian species and similar to great apes, undergoes regular cycles of formation and shedding, independent of the presence of the embryo in the endometrium. This process is also tightly controlled by various FGFs. In this review, we comprehensively compare diverse research decidualization models, delineate the trend of endometrial FGFs during the menstrual cycle, and provide a synopsis of endometrial diseases triggered by FGF dysregulation.
Humans ; Female ; Pregnancy ; Decidua/physiology* ; Animals ; Endometrium/physiology* ; Fibroblast Growth Factors/metabolism* ; Embryo Implantation ; Menstrual Cycle/physiology*

OBJECTIVES: To establish a prognostic model for primary liver cancer (PLC) using bioinformatics methods. METHODS: Based on the data from 404 patients in the Cancer Genome Atlas (TCGA) database, we constructed a prognostic model integrating the differentially expressed genes, anoikis, and immune-related genes (DAIs) using univariate Cox regression and the LASSO-Cox approach. The predictive ability of the model was evaluated using Kaplan-Meier method and receiver-operating characteristic curves, and a nomogram was developed to facilitate its clinical applications. Gene set enrichment analysis (GSEA) was performed to explore the associated pathways and relationship between the DAIs and the tumor immune microenvironment, and the half-maximal inhibitory concentration (IC₅₀) of liver cancer drugs was calculated using the "pRRophetic" R package. We also detected the expression of SEMA7A in paired tumor and adjacent tissues from liver cancer patients. RESULTS: We constructed and validated a prognostic model based on 7 DAIs (NR4A3, SEMA7A, IL11, AR, BIRC5, EGF, and SPP1), and obtained consistent results in both the TCGA training cohort and GEO validation cohort (GSE14520), where the patients in the low-risk group were characterized by more favorable clinical outcomes and immune status. By integrating this prognostic signature with clinical information, a composite nomogram was generated. Somatic mutation analysis showed that TTN, TP53, and CTNNB1 mutations accounted for the largest proportion of total mutations, and the patients in the low-risk-low-TMB group had higher survival rate. Drug sensitivity analysis revealed differences in sensitivity to chemotherapeutic agents between high- and low-risk groups and between TP53 mutations and non-mutations. In clinical tissue specimens, SEMA7A expression was significantly higher in liver cancer tissues than in the adjacent tissues. CONCLUSIONS We established a new prognostic model based on DAIs for predicting clinical outcomes and therapeutic response of patients with primary liver cancer.
Humans ; Liver Neoplasms/diagnosis* ; Prognosis ; Anoikis ; Nomograms ; Computational Biology ; Tumor Microenvironment ; Semaphorins/metabolism*

Objective: To determine the association between the intake of five major types of prepackaged foods and the growth and development of school aged children, so as to provide a theoretical basis for guiding school aged children and their parents to make healthy prepackaged food choices. Methods: Based on data from the South West China Childhood Nutrition and Growth Cohort (SCCNG), 381 children (6-11 years of age) were selected by stratified cluster sampling. Dietary intake and pubertal development were collected using questionnaires, and anthropometric measurements were obtained. Children were followed up until November 2022. Binary Logistic regression models were used to analyze the prospective association between prepackaged food intake and the growth and development of school aged children. Results: The total intake of the five major types of prepackaged foods was 316.1 (197.1,501.4) g/d. After 2 years of follow up evaluations, 16.5% of school aged children were shown to be overweight and obese. Early spermarche occurred in 12.6% of boys and early menarche occurred in 15.4% of girls. The following findings were suggested after adjusting for the mothers education level, average gross monthly family income, whether or not the family had one child only, geographic area of residence, body mass index Z score, average duration of daily exercise, and total dietary energy intake: convenience food intake might increase the risk of early spermarche ( OR =9.37); fruit and vegetable intake might decrease the risk of early spermarche and menarche ( OR =0.33,0.17); and fish, poultry, meat, and egg intake might increase the risk of early menarche ( OR =7.59)( P <0.05). Intake of the five types of prepackaged foods was not associated with being overweight or obese after adjusting for confounders ( OR =1.40, 0.57, 0.73, 1.33,1.57, P >0.05). Conclusions The relationship between intake of the five major types of prepackaged foods and pubertal development is inconsistent and no significant correlation was detected between the intake of prepackaged foods and overweight or obese children. Nutrition education should be strengthened to help children and their parents choose healthy prepackaged foods.

Hypoalbuminemia is one of the important clinical features of decompensated cirrhosis. As the disease progresses, not only does the total albumin concentration decrease, but so does the proportion of albumin that remains structurally and functionally intact. The structural and functional integrity of albumin is essential for its normal physiological role in the body. This led to the concept of "effective albumin concentration," which may be much lower than the total albumin concentration routinely measured clinically in patients with advanced cirrhosis. Liquid chromatography-tandem mass spectrometry, and electron paramagnetic resonance (EMR) are emerging technologies for effective albumin concentration detection, showing promising clinical application prospects, but research in patients with cirrhosis is still in the preliminary stage. Therefore, this article will comprehensively summarize the latest research on the aspects of effective albumin detection methods, liquid chromatography-tandem mass spectrometry, and electron paramagnetic resonance, as well as their applications.

The contents, application progress, application effect and optimization strategy of group pregnancy health care model were reviewed, in order to provide reference for the establishment of standardized intervention and health management practice strategies of rural women′s pregnancy care in line with China′s national conditions.

Objective:To explore the differences between the deep learning-based image reconstruction (DLIR) and the adaptive statistical iterative reconstruction V (ASiR-V) algorithms in the radiation dose and image quality of head and neck CT angiography (CTA).Methods:The data of 80 patients undergoing head and neck CTA due to vascular diseases in the head and neck were prospectively collected. These patients were randomly divided into groups A and B based on their examination sequence. The CTA images of group A were reconstructed based on ASiR-V 50%, with a tube voltage of 120 kV and a noise index of 11.0. In contrast, those of group B were reconstructed based on ASiR-V 50% (for group B1) and DLIR-H (for group B2), with a tube voltage of 80 kV and a noise index of 9.0. Then, the radiation doses and image quality of both groups were compared using the independent-sample t-test. The radiation doses, and both subjective and objective image quality of the two imaging method were compared through the Kruskal-Wallis test and the Wilcoxon rank-sum test. The independent- or paired-sample t-test was employed to measure inter-group vascular enhanced CT values, as well as signals and noise from regions of interest (ROIs), with signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs) calculated. Results:The effective doses of groups A and B were (0.77±0.08) and (0.45±0.05) mSv, respectively, with a statistically significant difference ( t = 21.96, P < 0.001). The vascular enhanced CT values, SDs, SNRs, and CNRs in the arch of the aorta, the initial and bifurcation parts of the common carotid artery, and the M1 segment of the middle cerebral artery showed statistically significant differences among groups A, B1, and B2 ( F = 67.69, 68.50, 50.52, 74.10, 63.10, 91.22, 69.16, P < 0.001). Additionally, statistically significant differences were observed in the subjective scores of image quality among groups A, B1, and B2 ( Z = 71.06, P < 0.05). Conclusions:The DLIR algorithm can further reduce the radiation dose in head and neck CTA examination while significantly reducing image noise and ensuring image quality, thus demonstrating high clinical application value.

Objective:To analyze the clinical features and immunotherapy responsiveness of patients with myelin oligodendrocyte glycoprotein immunoglobulin G-antibody associated disease (MOGAD) with epilepsy, and display the risk factors of epilepsy in MOGAD.Methods:Eighty-nine patients with MOGAD diagnosed at the First Affiliated Hospital of Zhengzhou University between October 2019 and May 2023 were enrolled and classified into 2 groups upon MOGAD with ( n=29) or without epilepsy ( n=60). The Expanded Disability Status Scale (EDSS) and Clinical Assessment Scale for Autoimmune Encephalitis (CASE) were used for evaluation of severity, and EDSS or CASE scores on the 30th day after first-line immunotherapy initiation lower than that on admission were defined as well treatment responsiveness. The differences of general data, clinical manifestations, cerebrospinal fluid (CSF) and peripheral blood biochemical examination results, and immunotherapy reactivity between the 2 groups were thoroughly explicated. In addition, the risk factors of epilepsy in MOGAD were analyzed by univariate and multivariate Logistic regression analysis. Results:Compared with patients with MOGAD without epilepsy, patients with MOGAD with epilepsy were characterized by lower age of onset [24.5(10.3, 34.0) years vs 11.0(6.5, 20.0) years, Z=-2.348, P=0.019], higher percentage of male patients [43.3%(26/60) vs 75.9%(22/29), χ 2=8.326, P=0.004], higher virus infection rate [28.3%(17/60) vs 51.7%(15/29), χ 2=4.645, P=0.031], higher incidence of prodromal symptoms [11.7%(7/60) vs 34.5%(10/29), χ 2=6.586, P=0.010], higher blood-brain barrier breakdown rate [35.0%(21/60) vs 58.6%(17/29), χ 2=4.458, P=0.035], higher percentage of CSF albumin level>450 mg/L [48.3%(29/60) vs 75.9%(22/29), χ 2=6.056, P=0.014] and higher creatine kinase level [45.50(28.50, 69.75) U/L vs 57.50(41.75, 97.25) U/L, Z=-2.349, P=0.019]; more epilepsy [0(0) vs 29/29 (100.0%), χ 2=89.000, P<0.001] and disturbance of consciousness [0(0) vs 6/29(20.7%), χ 2=10.224, P=0.001] as clinical manifestations, and more cerebral cortex lesions [30/60(50.0%) vs 25/29(86.2%), χ 2=10.856, P=0.001] on magnetic resonance imaging. Nevertheless, the patients with MOGAD without epilepsy were featured with more visual impairment [23/60(38.3%) vs 3/29(10.3%), χ 2=7.406, P=0.007], limb weakness [18/60(30.0%) vs 1/29(3.4%), χ 2=8.209, P=0.004], sensory disturbance [15/60(25.0%) vs 0(0), Fisher exact probability test, P=0.002] and more cervical cord lesions [22/60(36.7%) vs 4/29(13.8%), χ 2=4.946, P=0.026] on magnetic resonance imaging. Immunotherapy responsiveness was relatively poor in the MOGAD with epilepsy group [EDSS score lower than that on admission: 15/29(51.7%) vs 46/60(76.7%), χ 2=5.641, P=0.018; CASE score lower than that on admission: 16/29(55.2%) vs 47/60(78.3%), χ 2=5.072, P=0.024] compared with the MOGAD without epilepsy group. Male was the independent risk factor of epilepsy in MOGAD ( OR=7.078, 95% CI 1.709-29.326, P=0.007). Conclusions:Compared with patients with MOGAD without epilepsy, patients with MOGAD with epilepsy reported more male patients, lower age of onset and higher incidence of prodromal symptoms, blood-brain barrier dysfunction rate, virus infection rate, CSF albumin level and creatine kinase level; clinical phenotypes were mainly meningoencephalitis and more cerebral cortex lesions were shown on magnetic resonance imaging. MOGAD with epilepsy was closely related to poor immunotherapy responsiveness, and gender was found to be the independent risk factor for epilepsy in MOGAD.

Objective:To investigate the correlation between fibrinogen/albumin ratio (FAR) and overall burden of cerebral small vessel disease (CSVD).Methods:Patients with CSVD who visited the Department of Neurology, Zhengzhou Central Hospital Affiliated to Zhengzhou University from May 2023 to May 2024 were included retrospectively. All patients underwent MRI to evaluate the total CSVD burden score (range: 0-4) by cerebral microbleeds, white matter hyperintensities, lacunar and enlarged perivascular spaces. 0-1 point was the mild burden group, and 2-4 points were the moderate-to-severe burden group. FAR was calculated as serum fibrinogen (g/L)/albumin (g/L)×100%. Spearman correlation analysis and multivariate logistic regression analysis were used to determine the relationship between FAR and total CSVD burden. Results:A total of 261 patients with CSVD were enrolled, including 145 males (55.6%), aged 64.08±8.74 years. There were 110 patients (42.1%) in the CSVD mild burden group and 151 (57.9%) in the moderate-to-severe burden group. Spearman correlation analysis showed that there was a significant positive correlation between FAR and total CSVD burden scores ( r=0.385, P<0.001). Univariate analysis showed that the proportion of patients with diabetes, history of stroke or transient ischemic attack, as well as age, FAR, homocysteine and fibrinogen in the CSVD moderate-to-severe burden group were significantly higher than those in the mild burden group, while serum albumin and high-density lipoprotein cholesterol were significantly lower in the mild burden group (all P<0.05). Multivariate logistic regression analysis showed that higher FAR (odds ratio 1.433, 95% confidence interval 1.201-1.710; P<0.001) and homocysteine (odds ratio 1.093, 95% confidence interval 1.026-1.164; P=0.005) were significantly independently associated with the moderate-to-severe total CSVD burden. Conclusion:The level of FAR is closely associated with the severity of the total CSVD burden in patients with CSVD.

Objective:To analyze the relations of blood-brain barrier (BBB) integrity with clinical features and their response to immunotherapy in patients with autoimmune encephalitis (AE).Methods:One hundred and forty-seven AE patients confirmed in Department of Neurology, First Affiliated Hospital of Zhengzhou University from August 2015 to December 2021 were chosen; their clinical and laboratory data were collected retrospectively. In accordance with cerebrospinal fluid (CSF) albumin/serum albumin (QAlb) value of 7, patients were classified into normal BBB group ( n=101, QAlb value ≤7.00) and damaged BBB group ( n=46, QAlb value >7.00). Modified Rankin Scale (mRS) and Clinical Assessment Scale for Autoimmune Encephalitis (CASE) were used to evaluate the severity on admission and 30 d after first-line immunotherapy; and good immunotherapy responsiveness was defined as CASE or mRS scores 30 d after first-line immunotherapy lower than those at admission. Differences of general data, clinical manifestations, CSF and peripheral blood biochemical results, and response to immunotherapy between the two groups were compared and analyzed. Results:The damaged BBB group had significantly higher proportions of patients with decreased consciousness level (58.7% vs. 37.6%), increased CSF protein, increased immunoglobulin G (IgG) and increased 24 h intramural IgG synthesis rate, and significantly higher fibrinogen in peripheral blood than normal BBB group ( P<0.05). On 30 th d of treatment, mRS scores of patients in damaged BBB group were significantly higher than those of patients in normal BBB group ( P<0.05), and the differences of CASE scores and mRS scores before and after treatment in damaged BBB group were significantly lower than those in normal BBB group (0.50±0.46 vs. 3.24±2.93, 0.70±0.62 vs. 1.15±1.04, P<0.05). In damaged BBB group, good immunotherapy response rate in patients receiving single immunotherapy was significantly lower than that in patients receiving two or three combinations of first-line immunotherapy ( P<0.05). Conclusion:BBB integrity is closely related to clinical characteristics and response to immunotherapy of AE; combined first-line immunotherapy is recommended for AE patients with BBB injury.