ObjectiveTo explore the target of Erzhiwan in reducing myocardial injury in ovariectomized mice through non-targeted myocardial metabolomics combined with experimental verification. MethodsOvariectomized mouse model was selected， 40 female C57BL/6 mice were randomly divided into sham operation group， model group， estrogen group（estradiol valerate， 1.3×10^-4 g·kg^-1）， Erzhiwan low and high dose groups（3.12， 9.36 g·kg^-1）， with 8 mice in each group. Each administration group was given the corresponding dose of Erzhiwan by gavage， and the sham operation group and model group were given equal volume of distilled water by gavage for 12 weeks. Echocardiography was used to detect cardiac function， hematoxylin-eosin（HE） staining was used to observe myocardial morphological changes， and enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of estrogen， N-terminal pro-brain natriuretic peptide（NT-proBNP）， hypersensitive troponin T（hs-TnT）， total cholesterol（TC）， triglyceride（TG）， low density lipoprotein cholesterol（LDL-C）， high density lipoprotein cholesterol（HDL-C）， interleukin（IL）-1β， IL-18 and tumor necrosis factor-α（TNF-α）. The non-targeted metabolomics of mouse myocardium were analyzed by ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS）， and the differential metabolites and corresponding metabolic pathways were obtained. The mRNA expression levels of phosphatidylinositol 3-kinase（PI3K） and protein kinase B（Akt） in mouse myocardial tissues were detected by real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the protein expression levels of PI3K， Akt， phosphorylated（p）-Akt were detected by Western blot. ResultsCompared with the sham operation group， the model group showed abnormal cardiac function， increased myocardial fiber space， cardiomyocyte atrophy， sarcoplasmic aggregation， and occasional dissolution or rupture of muscle fiber， the level of estrogen in the serum was decreased， the levels of NT-proBNP， hs-TnT， IL-1β， IL-18， TNF-α， TG， TC and LDL-C were increased， and the level of HDL-C was decreased（P<0.01）. Compared with the model group， Erzhiwan could increase the level of estrogen， improve the abnormal cardiac function， reduce the pathological injury of myocardial tissue， decrease the levels of myocardial injury markers（NT-proBNP， hs-TnT） and inflammatory factors（IL-1β， IL-18， TNF-α）， decrease the levels of TG， TC， LDL-C， and increased the level of HDL-C（P<0.01）. The results of non-targeted myocardial metabolomics showed that 31 of the 162 differential metabolites between the model group and sham operation group were significantly adjusted after administration of Erzhiwan， which were mainly glycerol phospholipid metabolites. Pathway enrichment results showed that Erzhiwan mainly affected glycerophospholipid metabolic pathway， PI3K-Akt pathway， cyclic guanosine monophosphate（cGMP）-protein kinase G（PKG） pathway and other metabolic pathways. Compared with the sham operation group， the levels of phosphatidylcholine（PC， 11 types） and phosphatidylethanolamine（PE， 5 types） in mouse myocardial tissue of the model group were increased（P<0.05， P<0.01）， and the mRNA and protein expressions of PI3K and p-Akt were decreased（P<0.05， P<0.01）. Compared with the model group， the levels of PC（11 types） and PE（5 types） were decreased（P<0.05， P<0.01） in myocardial tissue of Erzhiwan group， the mRNA and protein expressions of PI3K and p-Akt were elevated（P<0.01）. ConclusionErzhiwan can alleviate the pathological injury of myocardium in ovariectomized mice， improve the abnormal cardiac function， improve lipid metabolism disorder， and reduce the levels of myocardial injury markers and inflammatory factors， which involves a number of signaling and metabolic pathways in the heart， among which glycerophospholipid metabolism pathway and PI3K/Akt pathway may have key roles.

It is believed that the root cause of vascular dementia lies in insufficient primal yang and weakness in the circulation of blood. The key pathological factors are the mutual stagnation of phlegm and blood stasis， and the obstruction of blood vessels. The general treatment principle is to tonify qi and promote yang， expel pathogenic factors， and unblock yang. This involves supplementing the innate and acquired yang qi of the spleen and kidneys， removing pathogenic factors like phlegm， turbidity， and blood stasis， in order to restore the function of yang qi and promote the circulation of blood and qi. The basic prescription for tonifying qi and promoting yang includes Heishunpian （Lycium Ruthenicum）， Zhichuanwu （Aconitum Carmichaelii）， Guizhi （Cinnamomum Cassia）， Renshen （Panax Ginseng）， and Huangqi （Astragalus Membranaceus）. Depending on the type of pathogenic excess， the treatment can be modified with Tongqiao Huoxue Decoction （通窍活血汤）， adding Yujin （Curcuma Longa） and Xiangfu （Cyperus Rotundus） to invigorate blood and promote yang， or with Fabanxia （Pinellia Ternata）， Chenpi （Citrus Reticulata）， Zhishi （Citrus Aurantium） plus Sijunzi Decoction （四君子汤） to resolve phlegm and promote yang. Both the root and branch are treated simultaneously. When yang qi is activated， blood and qi are nourished， and when pathogenic excess is expelled， the blood vessels are unblocked. This approach aims to provide a treatment strategy for vascular dementia.

Objective: To analyze the demographic characteristics of patients with red blood cell transfusion reactions, the usage of red blood cell preparations, and the differences in the composition ratio of adverse reactions based on multi-center data from the Haemovigilance Network, in order to reveal the clinical characteristics of red blood cell transfusion and its underlying issues. Methods: Clinical data of patients who experienced transfusion reactions after red blood cell transfusion in the Haemovigilance Network from 2018 to 2023 were collected. The demographic characteristics of patients who experienced transfusion reactions with different types of red blood cell preparations, the utilization of these preparations, and the differences of the composition ratios of transfusion reactions were analyzed. Count data were expressed as numbers (n) or percentages (%), and comparisons between groups were performed using the Chi-square test. Results: Red blood cell transfusion reactions were more common in females (53.56%), with the majority of patients aged 50-69 years (35.54%). The Han polulation accounted for the vast majority of patients (92.77%), and patients in the hematology and obstetrics/gynecology departments had a relatively high proportion of transfusion reactions (13.26% and 14.26%, respectively). Leukocyte-reduced red blood cells and suspended red blood cells were the most common types of transfusion reactions reported among red blood cell preparations. Allergic reactions and non-hemolytic febrile reactions were the most common transfusion reactions, and there were significant differences in the composition ratios of allergic reactions (χ =869.89, P<0.05) and non-hemolytic febrile reactions (χ =812.75, P<0.05) across various types of red blood cell preparations. Conclusion: There are differences in the demographic characteristics and composition ratio of transfusion reactions among different red blood cell preparations. The management of red blood cell transfusion reactions should be tailored to patient characteristics and conditions, and the selection and use of blood products should be optimized to reduce or avoid the occurrence of transfusion reactions, such as considering the use of washed red blood cells for patients with a history of transfusion allergies or those prone to allergies.

Objective: To investigate the role of ferroptosis in transfusion-related acute lung injury (TRALI) and evaluate the efficacy of the specific inhibitor Ferrostatin-1 (Fer-1), thereby to provide a basis for the prevention and treatment of TRALI. Methods: This study utilized a ”2-hit” model to induce TRALI in mice. The mouse model of TRALI was validated through survival curve analysis, lung tissue wet/dry weight ratio (W/D), myeloperoxidase (MPO) activity, and total protein concentration in lung tissue. Samples from the TRALI model group, LPS group, and control group (n=6) were collected. The occurrence of ferroptosis in TRALI was confirmed by measuring key ferroptosis indicators, including iron concentration in lung tissue, malondialdehyde (MDA) level, lipid peroxidation products (LPO) level, and expression levels of related proteins (GPX4, ACSL4). Additionally, a Fer-1 intervention group was added to evaluate its preventive and therapeutic effects. The survival rates and clinical symptoms of the four groups (n=6) were dynamically monitored, and the degrees of lung injury were assessed. Ferroptosis-related indicators were also measured to elucidate the protective mechanism of Fer-1. Results: A mouse model of TRALI was successfully established. Compared to the control and LPS groups, the TRALI group showed significantly higher levels of ferrous iron [(18.32±1.11) nmol/well, MDA [(14.68±0.96) μmol/L], and LPO [(1.60±0.02) μmol/L] in lung tissue (all P<0.01), along with a downregulation of GPX4 and an upregulation of ACSL4. Fer-1 pretreatment significantly reversed these abnormalities: the W/D ratio decreased to 4.01±0.43, and MPO activity significantly decreased [Fer-1 group: (21 606±4 235) pg/mL vs TRALI group: (30 724±2 616) pg/mL], the total protein concentration in lung tissue of the Fer-1 group decreased by approximately 40.8% compared to the TRALI group (all P<0.01). These changes indicate that the lung injury in mice was alleviated after treatment. Following Fer-1 intervention, ferrous iron concentration [(7.46±1.83) nmol/well] was restored to a level close to that of the control group [(5.48±0.70) nmol/well]. Lipid peroxidation tests further revealed that Fer-1 intervention reduced MDA and LPO levels by 35.8% and 29.4%, respectively (P<0.001). Additionally, the expression levels of GPX4 and ACSL4 proteins returned to near-normal levels in the treated mice (both P>0.05). Conclusion: The progression of TRALI is closely related to the activation of ferroptosis, characterized by iron overload, lipid peroxidation accumulation, and the imbalance of GPX4/ACSL4. Ferrostatin-1 significantly alleviates pulmonary edema and inflammatory damage by inhibiting the ferroptosis pathway, suggesting that targeting ferroptosis may provide a new therapeutic strategy for TRALI.

OBJECTIVE To explore the effect of superoxide dismutase （SOD） administration on the malignant behavior of PLC/PRF/5 liver cancer cells， and analyze the correlation between SOD and alpha-fetoprotein （AFP） expression， to provide new ideas for targeting AFP with SOD as a drug for hepatocellular carcinoma. METHODS Normal human liver cells L-02， AFP- negative human liver cancer cells HLE， and AFP-positive human liver cancer cells PLC/PRF/5 were used as experimental cells. Western blot assay and SOD activity detection kit were used to detect the expression of AFP， SOD and activity of SOD in cells before and after changing AFP expression； the effects of different concentrations of SOD [0 （control）， 0.188， 0.375， 0.75， 1.5， 3 U/mL] administration on the migration and proliferation of PLC/PRF/5 cells were detected using cell scratch assay and CCK-8 assay. The effects of SOD overexpression on the expression of malignant biological behavior-related proteins AFP and sarcoma virus protein （Src） in PLC/PRF/5 cells were detected using Western blot. RESULTS Compared with L-02 group and HLE group， the expression levels of SOD1 and SOD2， and SOD activity in PLC/PRF/5 cells were significantly reduced （P＜0.05）. After down-regulating AFP expression in PLC/PRF/ 5 cells， compared with PLC/PRF/5 group， the expression levels of SOD1 and SOD2， as well as SOD activity， were significantly increased in the PLC/PRF/5-shAFP group （low-expression） （P＜0.05）. After 48 hours of SOD treatment， compared with control group， the scratch healing rates of PLC/PRF/5 cells in the 0.375， 0.75， 1.5 and 3 U/mL SOD groups were significantly reduced （P＜0.05）； after 72 hours of SOD treatment， compared with control group， the scratch healing rates of PLC/PRF/5 cells in the 0.375， 0.75， and 1.5 U/mL SOD groups were significantly reduced （P＜0.05 or P＜0.01）. Compared with control group， proliferation rates of PLC/PRF/5 cells were significantly reduced in the 0.375， 0.75， 1.5 and 3 U/mL SOD groups （P＜0.05 or P＜0.01）. Compared with the PLC/PRF/5 group before up-regulating SOD1 and SOD2 expression， the expression levels of AFP and Src in the PLC/PRF/5-oeSOD1 and PLC/PRF/5-oeSOD2 groups （over-expression） after up-regulating SOD1 and SOD2 expression were significantly reduced （P＜0.05）. CONCLUSIONS A certain concentration of SOD can inhibit malignant behavior such as migration and proliferation of PLC/PRF/5 cells， and the expression level and activity of SOD are negatively correlated with AFP.

Objective To analyze the status of persistent human papillomavirus (HPV) infection and the distribution of viral subtypes in the Zhengzhou region. Methods Clinical data of 55239 patients who underwent HPV-DNA genotyping tests from 2018 to 2024 were collected. On the basis of HPV follow-up results, patients were divided into three groups: 849 cases of infection with the same HPV type, 255 cases of persistent infection with different HPV types, and 857 cases of transient HPV infection. Results Among the 9232 initially-screened patients who were positive with HPV, the high-risk HPV (HR-HPV) positive rate was 84.6% (7813/9232), and predominant subtypes were HPV-16 (20.8%), HPV-52 (17.2%), and HPV-53 (9.6%). The low-risk HPV (LR-HPV) positive rate was 15.4% (1419/9232), mainly HPV-81 (28.1%) and HPV-42 (27.0%). Among the 1961 follow-up cases, the rates of persistent and non-persistent infections with the same HPV type were 35.7% (701/1961) and 7.5% (148/1961), respectively. The rates of persistent and non-persistent infections with different HPV types were 10.9% (214/1961) and 2.1% (41/1961), respectively. Meanwhile, 43.7% (857/1961) tested negative upon follow-up. Among the 701 cases of persistent infection with the same HPV type, HR-HPV accounted for 85.7% (601/701), and LR-HPV accounted for 14.3% (100/701). Among the 214 cases of persistent infection with different HPV types, 89.7% (192/214) were high-risk transitions, and 10.3% (22/214) were low-risk transitions. Regardless of HPV types, HR-HPV was more likely to cause persistent infection than LR-HPV. In addition, over 60% of HR-HPV persistent infections resolved within 18 months, 30% developed into persistent infections, and only 15% of patients had persistent infections that last more than 24 months. Conclusion Persistent HPV infections are predominantly high-risk types. Most patients clear the infection within 18 months, approximately 30% develop persistent infections, and about 15% of patients have persistent infections that last more than 24 months. However, the HR-HPV persistent infection rates across different age groups slightly differ.

OBJECTIVE To develop a population pharmacokinetic （PPK） model for mycophenolate mofetil active metabolite mycophenolic acid （MPA） in children with primary IgA nephropathy， explore the factors affecting the pharmacokinetic parameters of MPA， and provide a basis for clinical individualized therapy. METHODS Retrospective collection was conducted on 636 concentrations and clinical data from 47 pediatric patients with primary IgA nephropathy. PPK analysis was carried out by using the nonlinear mixed-effects model； the covariates were tested with a stepwise method. Goodness-of-fit plots， Bootstrap and visual predictive check were employed to evaluate the final model. RESULTS The pharmacokinetics of MPA in children with IgA nephropathy in vivo conformed to the first-order absorption and elimination two-compartment model （objective function value of 3 276.31）. Covariate analysis suggested that body weight and albumin （ALB） levels were significant influencing factors on apparent clearance rate and apparent distribution volume. The typical values of PPK parameters of MPA in the final model were as follows： the central room had a distributed volume of 5.79 L， the clearance rate was 4.06 L/h， the volume of peripheral ventricular distribution was 430.93 L， the clearance rate between compartments was 15.40 L/h， the oral absorption rate constant was 1.29 h－1. After verification， most of the predicted corrected observed concentration points were within the 90% confidence interval of the predicted corrected simulated concentration， indicating that the MPA final model had good predictive performance. CONCLUSIONS The PPK model of MPA in children with primary IgA nephropathy is established in this study， identifying body weight and ALB levels are significant factors affecting MPA metabolism.

Objective:To distinguish Hedyotis diffusa Willd. and its common countrerfeit, Hedyotis corymbosa. and Hedyotis tenelliflora. by analyzing and comparing their macroscopical identification, microscopic character and HPLC fingerprints. Methods:The features of macroscopical identification, microscopic character including cross-sections of stem, leaf, fruit and seed, and herbal powders were observed in the three samples by traditional methods. The difference of chromatographic peaks among the three samples were also analyzed by HPLC methods.Results:The stems of Hedyotis diffusa Willd. were cylindrical, and the capsules were solitary or double born in the leaf axils, oblate, 2-3 mm in diameter, with a long petiole; the Hedyotis corymbosa. and Hedyotis tenelliflora. were tetragonal, and the Hedyotis corymbosa. was 2-5 capsules born in leaf axils in corymbose inflorescences, globular, 1-1.5 mm in diameter, with a slender petiole; the Hedyotis tenelliflora. were 1-3 capsules clustered in the leaf axils, ovoid with longitudinal ribs around the margin, about 1.5 mm in diameter, without the long petiole, about 1.5 mm in diameter, sessile, the edge of the leaf drying revolute long needle-like. Under the identification, the cross section of the Hedyotis diffusa Willd. stem was almost round, the middle vein of the leaves was protrusion below, the inner pericarp fiber layer consisted of two layers of fiber cells, the surface of the seed coat cells was polygon, and the wall was densely covered with small reddish brown or yellow-brown warty spots. The cross section of the Hedyotis corymbosa. stem was quadrilateral, the surface of the seed coat cell was polygon, the wall was wavy and curved, and there was no warty point on the wall. The middle veins of the Hedyotis tenelliflora. were slightly sunken in the upper part, but not protruding in the lower part; the endocarp fiber layer consisted of 8 to 13 layers of fiber cells. Moreover, the HPLC fingerprint analysis demonstrated substantial dissimilarities in the characteristic peaks of these herbs. Conclusion:The traditional and modern analysis technology show that there are some differences in the characteristics, microscopical cross section, the powder characteristics, which can effectively distinguish the Hedyotis diffusa Willd. and its two local varieties.

Objective To explore EEG characteristics and the therapeutic effect in children with electrical status epilepticus during slow sleep(ESES).Methods The eligible ESES cases in our center from 2014 to 2020 were included.The age at diagnosis of ESES,the duration of ESES,spike wave index(SWI)during wakefulness and the distribution of spike wave during the period of ESES,age at seizure onset,the clinical syndromes and the outcomes after treatment were analyzed.The ESES cases were divided into 4 groups according to the distribution of spike wave:focal ESES,unilateral ESES,bilateral asymmetric ESES,multiple foci ESES.The SWI during the awake stage were divided into 3 groups based on the different rates:≤20%,21%～49%,≥50%.The therapeutic outcomes were classified into three groups:satisfactory response,seizure control and ineffective.Results 50 cases were included,with 32 males and 18 females.The average onset age of ESES was 6 years and 7 months,and the average duration of ESES was 28 months.A significant correlation between the distribution of ESES and the thera-peutic effects was found,bilateral asymmetric ESES had a good therapeutic effects,while multiple foci ESES showed a poor therapeutic effects.The duration of ESES was significantly correlated with therapeutic effects,and the efficacy was worse when the duration was longer than 1 year.A significant relationship between the SWI during wakefulness of ESES and the therapeutic effects was detected,the patient with SWI≤20%during wakefulness had a good therapeutic effect.There was a negative correlation between the onset age of ESES and the duration of ESES and SWI index during wakefulness.There was a positive correlation between the duration of ESES and SWI index during wakefulness.Conclusion Our results suggest that onset age,distribution,duration and SWI during wake-fulness of ESES were correlated with therapeutic outcomes,The patient with SWI≤20%during wakefulness had a good therapeutic effect and have unfavorable outcomes with ESES last more than 1 year.The earlier onset of ESES,the longer duration of ESES and higher SWI during wakefulness will be showed..

Objective To investigate the effects of icariin on high glucose-induced autophagy and apoptosis of podocytes,and the regulating effects on mammalian target of rapamycin(mTOR)/serine-threonine kinase(Akt)/cyclic adenosine monophosphate response element binding protein(CREB)pathway.Methods The mouse podocytes MPC5 were taken and divided into five groups:normal control group(5.5 mmol·L-1 glucose),high glucose group(30 mmol·L-1 glucose),icariin group(30 mmol·L-1glucose+5 μmol·L-1icariin),GDC-0349 group(30 mmol·L-1glucose+50 μmol·L-1 GDC-0349),icariin+GDC-0349 group(30 mmol·L-1 glucose+5 μmol·L-1 icariin+50 μmol·L-1 GDC-0349).Cultured for 48 hours,the tetramethylazozolium salt method was used to detect the viability of MPC5 cells;acridine orange staining was used to observe the autophagy of MPC5 cells;apoptosis of MPC5 cells was detected by flow cytometry;Western blotting was used to detect the expression of autophagy[microtubule associated protein one light chain 3(LC3)II,LC3Ⅰ,autophagy-related protein(Beclin-1)],apoptosis[Bcl-2 related X protein(Bax),B cell lymphoma-2(Bcl-2)]and mTOR/Akt/CREB pathway-related proteins of MPC5 cells.Results Compared with the normal control group,the cell viability,expression levels of Bcl-2,phosphorylated mTOR(p-mTOR)/mTOR,phosphorylated Akt(p-Akt)/Akt,phosphorylated CREB(p-CREB)/CREB protein of MPC5 cells in the high glucose group were significantly decreased(P＜0.05),the autophagy ability was enhanced,the autophagosome showed orange fluorescence,and the apoptosis rate,LC3Ⅱ/LC3Ⅰ,Beclin-1,Bax protein expression levels were significantly increased(P＜0.05).Compared with the high glucose group,the cell viability,LC3Ⅱ/LC3Ⅰ,Beclin-1,Bcl-2,p-mTOR/mTOR,p-Akt/Akt,p-CREB/CREB protein expression levels of MPC5 cells in icariin group were significantly increased,the autophagy ability was further enhanced,the number of autophagosomes was increased,the autophagosomes showed brick red fluorescence(P＜0.05),the apoptosis rate and Bax protein expression level were significantly decreased(P＜0.05),and the cell viability,LC3Ⅱ/LC3Ⅰ,Beclin-1,Bcl-2,p-mTOR/mTOR,p-Akt/Akt and p-CREB/CREB proteins expression levels of MPC5 cells in GDC-0349 group were significantly decreased,the autophagy ability was weakened,the number of autophagosomes was reduced,the autophagosomes showed orange fluorescence(P＜0.05),and the apoptosis rate and Bax protein expression level were significantly increased(P＜0.05);icariin+GDC-0349 could reverse the effect of icariin on high glucose induced MPC5 cells(P＜0.05).Conclusion Icariin promotes elevated glucose-induced podocyte autophagy and inhibits apoptosis by activating the mTOR/Akt/CREB pathway.