OBJECTIVE To establish population pharmacokinetic model of levetiracetam （Lev） for Chinese patients with post- stroke epilepsy （PSE）， and provide reference for formulating individualized dosing regimens for Lev therapy in this specific population. METHODS Blood concentration data and clinical diagnosis and treatment information of PSE patients meeting the inclusion criteria were retrospectively collected and divided into model group and validation group at an 8∶2 ratio using a random number method. Based on the model group data， a population pharmacokinetic model was developed using nonlinear mixed-effects modeling. Internal evaluation was performed through goodness-of-fit tests and bootstrap analysis， while external validation was conducted using the validation group data. RESULTS A total of 75 blood concentration measurements from 70 PSE patients were collected， with 60 measurements from 55 patients used for model development and 15 measurements from 15 patients reserved for external validation. The final model estimated a population typical value of clearance at 2.98 L/h. Estimated glomerular filtration rate， daily dose， and homocysteine level significantly influenced clearance of Lev （P＜0.01）. The model demonstrated satisfactory predictive performance， as evidenced by goodness-of-fit tests， bootstrap analysis， and external validation results. CONCLUSIONS Daily dose， estimated glomerular filtration rate， and homocysteine level are identified as significant covariates influencing Lev clearance in Chinese PSE patients. When making clinical decisions， comprehensive consideration should be given to the patient’s treatment response， physiological and pathological conditions， and the occurrence of adverse reactions， etc. The dosage of Lev should be adjusted based on the results of population pharmacokinetic model.

Osteoarthritis(OA)is a common concern over the world.Garlic is a kind of natural herbal medicine,and its active ingredients have shown some anti-inflammatory,antioxidant,anti-catabolic,analgesic and other phar-macological effects.Garlic and its active components alleviate the inflammatory response of OA by inhibiting the ex?pression of inflammatory factors and signal pathways such as NF?κB and PI3K/Akt.They slow down the progression of OA by inhibiting the expression of extracellular matrix(ECM)degrading enzymes.Additionally,they reduce the oxidative damage of joints by upregulating the expression of antioxidant enzymes.Moreover,the active components of garlic can relieve OA pain by activating the potassium ion pathway(Kv7),ATP?sensitive potassium channel(K?ATP),and the nuclear factor erythroid 2?related factor 2(Nrf2)/heme oxygenase 1(HO?1)?NAD(P)H:qui?none oxidoreductase 1(NQO1)signaling pathway.

BACKGROUND:The repair process of skin trauma is complex and susceptible to infection,easy to lead to poor healing,is the current difficulty and hot spot in wound repair research,and has received extensive attention in the fields of traditional Chinese medicine and tissue engineering. OBJECTIVE:To investigate the effect of moxibustion and reduced graphene oxide/cerium oxide nanocomposite on promoting the healing of infectious wounds. METHODS:(1)Reduced graphene oxide/cerium dioxide nanocomposites with mass ratios of 2:1,1:1 and 1:2 were synthesized by hydrothermal method.The resulting composites were recorded as G2C1,G1C1 and G1C2,respectively.The photothermal properties,cytotoxicity and antibacterial properties of the three kinds of materials were tested.After taking moxa sticks,three kinds of moxibustion distances were set(3.0-3.5 cm,recorded as moxibustion 1;2.5-3.0 cm,recorded as moxibustion 2;2.0-2.5 cm,recorded as moxibustion 3).Moxibustion was applied to the surface of human skin for 10 minutes to detect the photothermal properties.The antibacterial properties of moxibustion were tested at three different distance intervals.Simultaneously,the back body surface infrared imaging of rats with different mass concentrations of G1C1 material,moxibustion(three kinds of moxibustion distances)and moxibustion 2+G1C1 material was detected.(2)Sixty male Sprague-Dawley rats were selected to model the wound of Staphylococcus aureus infection.48 hours later,they were randomly divided into 10 groups with 6 rats in each group:control group(did not receive any treatment),mupirocin group,moxibustion 2+G1C1 group,moxibustion 1 group,moxibustion 2 group,moxibustion 3 group and 60,80,100,and 120 μg/mL G1C1 groups(The G1C1 group was given 808 nm near-infrared laser irradiation for 10 min/time,and the G1C1 suspension was loaded on the wound surface before each treatment.Each group of moxibustion underwent in-situ suspension moxibustion,and the intervention time was 10 min/time.Moxibustion 2+G1C1 group was loaded with G1C1 suspension on the wound surface before each treatment,and moxibustion was suspended in situ with moxa strips,and the intervention time was 10 min/time).The frequency of treatment was 2 days once.Wound healing,wound colony count and repair were detected after 7 days of intervention. RESULTS AND CONCLUSION:(1)The three kinds of reduced graphene oxide/cerium dioxide nanocomposites had good photothermal properties,and the higher the mass concentration of the composites,the better the photothermal properties.The temperature of the moxibustion 2 group reached 47.6 ℃for 10 minutes without causing thermal damage,which was more suitable for animal experiments.The results of co-culture with NIH-3T3 cells exhibited that 60,80,and 100 μg/mL G1C1 had good biocompatibility.The results of a co-culture experiment with Staphylococcus aureus suspension displayed that G2C1,G1C1 and G1C2 had good antibacterial activity,among which G1C1 group demonstrated excellent antibacterial performance,and the antibacterial rate reached 100％when its mass concentration was 80 μg/mL.60-120 μg/mL G1C1 could effectively remove Staphylococcus aureus biofilm,and the higher the material mass concentration,the better the removal effect.Moxibustion could also effectively remove Staphylococcus aureus biofilm,and the closer the moxibustion was,the better the removal effect.(2)Compared with the control group,the wound area of the mupirocin group,moxibustion 2 group,moxibustion 2+G1C1 group and 80,100 μg/mL G1C1 groups was significantly reduced on day 7 of treatment,and the quality of wound repair was better.Mupirocin,G1C1,moxibustion and moxibustion 2+G1C1 could effectively remove the residual bacteria on the wound surface,and the higher the mass concentration of G1C1,the lower the residual bacteria.Among them,the wound repair efficiency and bacterial residue of 80 μg/mL G1C1 group and moxibustion 2 group were very similar,and the wound repair efficiency of both was better than that of mupirocin group.In addition,it was also observed that the combination of materials and moxibustion had a better ability to clear wound bacteria than that used alone.(3)The results confirm that moxibustion,reduced graphene oxide/cerium dioxide nanocomposites and their combination have good anti-infection and wound healing effects.

Objective To study the effect of changes in estradiol(E2)levels on the reproductive outcomes of pa-tients with polycystic ovary syndrome(PCOS)undergoing controlled ovarian stimulation(COS)with gonadotropin-releasing hormone antagonist(GnRH-ant)protocol.Methods A retrospective study was conducted involving 338 patients with polycystic ovary syndrome(PCOS)infertility who underwent GnRH-ant protocol for controlled ovarian hyperstimulation followed by in vitro fertilization(IVF)or intracytoplasmic sperm injection(ICSI),and subse-quently underwent their first frozen-thawed embryo transfer(FET).The clinical data of these patients were ana-lyzed.Patients were grouped based on the changes in serum E2 levels on the first and fourth day of GnRH-ant ad-ministration(blood samples collected before GnRH-ant injection):the E2 elevation group(Group A,E2 value in-creased more than 30％,165 cases),the E2 stable group(Group B,E2 rate of change was within-30％～30％,162 cases),and the E2 decline group(E2 value declined more than 30％,11 cases,not included in statistical a-nalysis due to small sample size).The differences in demographic characteristics,ovulation induction outcomes,embryo outcomes and clinical pregnancy-related indicators were analyzed between Groups A and B.Results There were no statistically significant differences in basic information such as age,duration of infertility,body mass index(BMI),basal endocrine levels,and anti-Müllerian hormone(AMH)levels between groups A and B.Regarding embryo characteristics,there were no statistically significant differences in fertilization method and number of trans-ferred embryos between groups A and B.However,group A had a higher total number of retrieved oocytes,normal fertilization rate,number of high-quality embryos,and rate of high-quality embryos compared to group B,with sta-tistically significant differences(P＜0.05).In terms of clinical pregnancy outcomes,there were no statistically significant differences in the incidence of severe ovarian hyperstimulation syndrome(OHSS)between groups A and B.However,group A had higher rates of clinical pregnancy,implantation,and live birth compared to group B,with statistically significant differences.Group A also had a lower rate of early miscarriage compared to group B,with statistically significant differences.Conclusion Choosing the GnRH-ant protocol for IVF/ICSI-FET in PCOS patients,if the blood E2 level increases by more than 30％after 4 days of adding the antagonist(blood sample col-lected before administering GnRH-ant),the clinical pregnancy outcome will be better.

Objective To investigate the effect of growth hormone(GH)pretreatment on the improvement of eu-ploid and pregnancy outcome.Methods A prospective analysis was conducted on 134 patients undergoing preim-plantation genetic testing for aneuploidy(PGT-A),among whom 30 patients were self-controlled and 104 patients were inter-group controlled.According to whether GH was added,the patients were divided into GH pretreatment group and GH non-pretreatment group.GH pretreatment included subcutaneous injection of GH 2U/day for 4-6 weeks before the start of gonadotropin(Gn),and the dose was doubled on the day of Gn until the trigger day.GH non-pretreatment meant no GH treatment,GH pretreatment was given when the previous PGT-A cycle failed within one year when the PGT-A was performed again,forming the self-control group.The basic situation,blastocyst situa-tion and pregnancy outcome were compared between the groups by inter-group and self-control.Results No matter in the group control or self-controlled group,the endometrial thickness on the day of HCG,ovarian sensitivity index(OSI),number of oocytes obtained,MII oocytes,2PN number,2PN fertilization rate,available oocyte rate,num-ber of biopsy blastocysts,number of euploid blastocysts,euploid blastocyst rate,and at least one euploid rate sig-nificantly increased after GH pretreatment,with statistically significant differences(P＜0.05).The total amount of Gn,Gn days,number of mosaic blastocysts,and mosaic blastocyst rate were not significantly changed after GH pretreatment,with no statistically significant differences.The implantation rate and clinical pregnancy rate in-creased after GH pretreatment,but with no statistically significant differences.Conclusion GH pretreatment can significantly improve the number and rate of euploid embryos in patients undergoing PGT-A,and has a tendency to improve pregnancy outcome.

Objective:To retrieve and summarize the best evidence for nursing of hematopoietic stem cell reinfusion in children.Methods:Clinical decisions, guidelines, recommended practices, evidence summaries, systematic reviews, and expert consensuses on nursing of hematopoietic stem cell reinfusion in children were searched in Chinese and English databases as well as related websites such as British Medical Journal (BMJ) Best Practice, National Institute for Health and Clinical Excellence, National Guideline Clearinghouse, Guidelines International Network, Scottish Intercollegiate Guidelines Network, Joanna Briggs Institute Evidence-Based Health Care Center Database, UpToDate, CINAHL, Embase, PubMed, China National Knowledge Infrastructure, WanFang Data, and VIP. The search period was from database establishment to March 2023. Two researchers independently conducted literature quality evaluation, identified the included literature, extracted evidence item by item, and translated, organized and summarized the evidence.Results:A total of nine articles were included, including two clinical decisions, two expert consensuses, four guidelines, and one evidence summary. 24 pieces of evidence were summarized from six aspects, consisting of child preparation, stem cell preparation, item preparation, nursing during reinfusion, nursing after reinfusion, and evaluation and education.Conclusions:The best evidence for nursing of hematopoietic stem cell reinfusion in children involves a wide range of aspects. Managers, clinical medical and nursing staff should apply evidence based on specific medical situations in order to safely and reasonably perform hematopoietic stem cell reinfusion.

Objective : To analyze the pregnancy outcome of preimplantation genetic testing for aneuploidy (PGT-A) in cycles with different indications． Methods : The clinical information of 549 couples who underwent PGT-A were retrospectively analyzed．The cycles were divided into 6 groups according to the indication for PGT-A，namely : recurrent pregnancy loss group(n = 304) ，repeated implantation failure group(n = 57) ，advanced age group( ≥38 years old，n = 80) ，history of adverse pregnancy group(chorionic trisomy or adverse pregnancy，n = 24) ，male factor infertility group (n = 67) ，and abnormal sex chromosome number group (n = 17) ．The basic information，the number of retrieved oocytes，embryo biopsy result and pregnancy outcome were compared among different indication groups. Results: The average age and days of gonadotropin ( Gn) used among the six groups were statistically different (P＜0. 001) ．The average number of retrieved oocytes，the rate of good-quality embryos，mosaic embryos， abnormal embryos and normal embryos，the average ovarian sensitivity index ( OSI) among the six groups were statistically different (P = 0. 03，P ＜0. 001，P = 0. 03，P ＜0. 001，P ＜0. 001，P ＜0. 001 ) ．Advanced age group had the highest rate of abnormal embryos，the least average number of retrieved oocytes，the lowest OSI and the lowest rate of normal embryos．There were statistical differences in clinical pregnancy rate，ongoing pregnancy rate and cumulative pregnancy rate per oocyte retrieved cycle (P＜0. 001) among the six groups，but there were no statistical differences in clinical pregnancy rate，ongoing pregnancy rate per transfer cycle and cumulative pregnancy rate among the five groups except for the male factor infertility group． Conclusion PGT-A can detect euploid embryo to transfer thereby improving pregnancy efficiency．The advanced age women have normal embryo to transfer and can obtain a better pregnancy rate，which may shorten their time of“take- baby -home ”．At the same time， PGT-A can significantly improve the pregnancy outcome of those with male factor infertility.

Objective:To observe and determine the gene mutation site and clinical phenotype of a NDP gene mutant family, and provide a basis for the prenatal diagnosis of offspring. Methods:A pedigree investigation study. Two patients and 6 family members of a third-generation Han family with NDP gene mutation who were admitted to the Maternal and Child Health Hospital of Gansu Province from July 2019 to December 2021 were included in the study. The patients and their parents underwent the examination of pupil light reflex, strip light imaging, visual acuity evaluation, fundus color photography, and wide-field fluorescein fundus angiography (FFA). Peripheral blood of all the subjects was collected, the pathogenic genes were screened by whole exome sequencing, and NDP genes were detected by amplification of multiple ligated probes. DNA prenatal diagnosis was performed by amniocentesis at 19th weeks of the mother's third gestation. Results:Proband (Ⅲ1), male, 4 years old, full term natural delivery. At about 40 days after birth, B-mode ultrasonography indicated total retinal detachment in both eyes. Normal hearing and intelligence. Fundus examination was not performed. First sibling of proband (Ⅲ2, big younger brother), ophthalmologic examination 30 days after birth, retinal detachment in both eyes. Proband's mother (Ⅱ2) had unvascularized peripheral temporal retina in both eyes. Wide-angle FFA examination showed no vascularization of the peripheral temporal retina in both eyes, and slight leakage of peripheral vascular fluorescein. The proband's second sibling (Ⅲ3, little younger brother) was screened for neonatal eye disease 1 day after birth. No abnormalities were observed outside both eyes. Cornea and lens transparent. No abnormalities were observed in the optic disc and macula in both eyes. No vascular curvature was observed in the peripheral retina. The results of gene detection showed that there was hemizygote deletion in exon 2 of NDP gene of the proband (Ⅲ1) and its big younger brother (Ⅲ2). His mother (Ⅱ2) had heterozygosity deletion in exon 2 of NDP gene. The phenotype and genetic test results of the proband's father (Ⅱ1), uncle (Ⅱ3), maternal grandfather (Ⅰ1) and maternal grandmother (Ⅰ2) were not abnormal. Conclusions:The hemizygote deletion in exon 2 of NDP gene is a pathogenic variation in the native family. The clinical phenotypes of different genders are different. Prenatal diagnosis is an effective way to block hereditary diseases in families.

Objective:To explore the application of microvascular flow imaging (MVFI) combined with high-frequency ultrasonography in children with haemophilic arthropathy A (HAA).Methods:Retrospective study.A total of 82 children diagnosed with HAA in the First Affiliated Hospital of Zhengzhou University from October 2018 to October 2020 were recruited.The elbow, knee and ankle joints of each child were examined by high-frequency ultrasonography.The numbers of thickened synovial joints were recorded.Blood flow signals of the thickening of synovial joints was checked by the MVFI and power Doppler ultrasound (PDUS), respectively.Color flow signals were graded by the semi-quantitative scoring systems.The chi- square test and independent multi-group ordinal multi-category rank-sum test were used to compare the differences of MVFI and PDUS in the display of thickened synovial blood flow. Results:A total of 254 joints were involved in 82 children with HAA, including synovial hypertrophy in 188 joints, hydrops articuli in 146 joints, fibrotic septa in 66 joints, cartilage damage in 63 joints, haemosider indeposition in 45 joints, bone erosion in 25 joints, osteophytes in 15 joints and bone remodeling in 8 joints.Grade Ⅱ synovial thickened joints were the most common.The proportion of blood flow signals detected by PDUS in thickened synovial membranes was significantly higher than that detected MVFI (52.66% vs.70.21%, χ2=12.225, P<0.05). Numbers of grade 0 and Ⅰ joints with thickened synovial membranes detected by MVFI were less than those of PDUS, while the opposite result was obtained in detecting grade Ⅱ and Ⅲ joints ( H=21.158, P<0.05). Compared with PDUS, MVFI more sensitively visualized the blood flow of the thickened synovial membrane. Conclusions:MVFI can more prominently detect the thickened synovial blood flow in children with HAA.A combined application of MVFI and high-frequency ultrasonography contributes to the evaluation of children with HAA.

The local microenvironment is essential to stem cell-based therapy for ischemic stroke, and spatiotemporal changes of the microenvironment in the pathological process provide vital clues for understanding the therapeutic mechanisms. However, relevant studies on microenvironmental changes were mainly confined in the acute phase of stroke, and long-term changes remain unclear. This study aimed to investigate the microenvironmental changes in the subacute and chronic phases of ischemic stroke after stem cell transplantation. Herein, induced pluripotent stem cells (iPSCs) and neural stem cells (NSCs) were transplanted into the ischemic brain established by middle cerebral artery occlusion surgery. Positron emission tomography imaging and neurological tests were applied to evaluate the metabolic and neurofunctional alterations of rats transplanted with stem cells. Quantitative proteomics was employed to investigate the protein expression profiles in iPSCs-transplanted brain in the subacute and chronic phases of stroke. Compared with NSCs-transplanted rats, significantly increased glucose metabolism and neurofunctional scores were observed in iPSCs-transplanted rats. Subsequent proteomic data of iPSCs-transplanted rats identified a total of 39 differentially expressed proteins in the subacute and chronic phases, which are involved in various ischemic stroke-related biological processes, including neuronal survival, axonal remodeling, antioxidative stress, and mitochondrial function restoration. Taken together, our study indicated that iPSCs have a positive therapeutic effect in ischemic stroke and emphasized the wide-ranging microenvironmental changes in the subacute and chronic phases.
Animals ; Cell Differentiation ; Disease Models, Animal ; Ischemic Stroke ; Proteomics ; Rats ; Stem Cell Transplantation/methods* ; Stroke/therapy*