OBJECTIVES: To explore the relationship between white matter injury (WMI) and cerebral perfusion in preterm infants using arterial spin labeling (ASL). METHODS: A total of 293 preterm infants (gestational age <34 weeks) hospitalized at the Third Affiliated Hospital of Zhengzhou University between June 2022 and June 2024 were included. After achieving clinical stability, the infants underwent brain magnetic resonance imaging (MRI) and ASL. Based on MRI findings, infants were classified into WMI (n=66) and non-WMI (n=227) groups. Cerebral perfusion parameters were compared between groups, and the association between WMI and perfusion alterations was evaluated. RESULTS: The WMI group showed a higher incidence of mild intraventricular hemorrhage (IVH) than the non-WMI group (P<0.05). Significantly lower cerebral perfusion was observed in the WMI group across bilateral frontal, temporal, parietal, and occipital lobes, as well as the basal ganglia and thalamus (P<0.05). After adjusting for gestational age, corrected gestational age at ASL scan, and mild IVH, WMI remained significantly associated with reduced regional perfusion (P<0.05). CONCLUSIONS WMI in preterm infants correlates with localized cerebral hypoperfusion. ASL-detected perfusion abnormalities may provide novel insights into WMI pathogenesis.
Humans ; White Matter/blood supply* ; Infant, Newborn ; Spin Labels ; Infant, Premature ; Female ; Male ; Cerebrovascular Circulation ; Magnetic Resonance Imaging

Objective To investigate the effect of esketamine on postoperative anxiety and cognitive function in gynecological malignant tumor patients with preoperative anxiety and cognitive decline.Methods Eighty-nine patients were selected for resection of gynecological malignant tumors,aged 18-64 years,BMI 18-28 kg/m2,ASA physical status Ⅱ or Ⅲ,the hospital anxiety and depression scale(HADS)anxiety subscale score≥8 points and montreal cognitive rating scale(MoCA)＜26 points 1 day before surgery.The patients were divided into two groups using the random number table method:the esket-amine group(group S,n = 45)and the normal saline group(group C,n = 44).In group S,esketamine 0.2 mg/kg was injected intravenously during anesthesia induction,0.25 mg·kg-1·h-1 was injected by pump during anesthesia maintenance,and esketamine 100 mg was used in the postoperative analgesic pump.Group C was given the same volume of normal saline during anesthesia induction,maintenance and PCIA analgesia,and other medications were the same as those in group S.HADS and MoCA were used to evaluate patients'anxiety and cognitive function 1 day before surgery and the 1 day and 3 days after surgery.The con-centration of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),S100 calcium-binding protein(S100β),and brain-derived neurotrophic factor(BDNF)were detected 1 day before surgery and 3 days af-ter surgery.The intraoperative dosage of remifentanil,ephedrine use rate,Ramsay sedation score 10 minutes after admission to PACU,extubation time,the number of total and effective compressions of PCIA within 48 hours after surgery,postoperative remedial analgesia,and the occurrence of adverse reactions,such as hy-pertension,hypotension,nausea and vomiting,chill,dizziness,and fever within 48 hours after surgerywere recorded.Results Compared with group C,the incidence of anxiety were significantly reduced and MoCA cognitive score were increased 1 day and 3 days after surgery,the concentrations of TNF-α,IL-6,and S100β were significantly reduced,the concentration of BDNF was significantly increased,the dosage of remifentanil was significantly reduced,the sedation score of Ramsay was significantly increased,the number of total compressions and effective compressions of PCIA within 48 hours after surgery was significantly re-duced,and postoperative fever was significantly reduced in group S(P＜0.05).There were no statistically significant differences in ephedrine use rate,extubation time,postoperative remedial analgesia rate,the in-cidence of other adverse reactions,such as hypertension,hypotension,nausea and vomiting,chills and diz-ziness within 48 hours after surgery between the two groups.Conclusion Esketamine can decrease the con-centrations of inflammatory factors and reduce nerve damage,help relieve anxiety and cognitive function of patients with gynecological malignant tumors.

Objective:To investigate the effect of construction and practice of problem-based learning(PBL)case database based on post competency for postgraduates majoring in Clinical Pharmacy.Methods:Through collective discussion,the case theme selection,case design and teaching process were clarified,and the case database was constructed.Students in grade 2021 received the traditional teaching method and students in grade 2022 received case-based teaching method.The teaching effect was evaluated according to the training objectives.Results:Compared with students in grade 2021,the students in grade 2022 showed an improvement trend in various evaluation indicators such as stimulating learning interest,literature review ability,problem analysis ability,problem-solving ability,team collaboration ability,and final exam score(P＜0.05).Conclusion:The PBL teaching method based on post competency case is conducive to improving the practical ability to find,analyze and solve practical problems in practical work of postgraduates majoring in Clinical Pharmacy.

MELAS syndrome is a genetic disease caused by mutations in mitochondrial DNA(mtDNA)or nuclear DNA.Eighty percent of the cases are caused by m.3243A>G mutation.Heteroplasmy,defined as the presence of both normal and mutant mtDNA in cells,is related with the severity of MELAS syndrome.This article reviews the research in mtDNA heterogeneity related to MELAS syndrome,aiming to provide an insight into new therapies for the syndrome.

【Objective】 To evaluate the therapeutic effect of probiotics on core symptoms in patients with autism spectrum disorder (ASD), in order to provide theoretical basis for the treatment and intervention of ASD. 【Method】 Articles published from January 2000 to May 2023 on the effect of probiotics on core symptoms in ASD children were retrieved from 7 databases, including Chinese Biomedical Literature Service System (SinoMed), Wanfang Data Knowledge Service Platform, VIP Citation Database, and China National Knowledge Infrastructure (CNKI), PubMed, Embase, and Web of Science.Meta-analysis was performed using RevMan 5.4.Effect size, combine heterogeneity test sensitivity analysis and subgroup analysis were calculated. 【Result】 Totally 10 studies with 343 patients were included in this Meta-analysis.Meta-analysis showed that there was statistically significant difference in ASD core symptom score between the intervention group and the control group (SMD=-0.34, 95%CI: -0.55 - -0.12, P<0.05).Subgroup analysis showed that the efficacy of the trial conducted in Asian populations was not significant (SMD=-0.32, 95%CI: -0.63 - 0.00, P=0.05).In Caucasian populations, the therapeutic effect was significant (SMD=-0.35, 95%CI: -0.65 - -0.06, P<0.05).Grouped by age, it was found that the efficacy was not significant in trials involving adults (SMD=-0.12, 95%CI: - 0.57 - 0.33, P=0.61), but significant in trials involving only minors (SMD=-0.40, 95%CI: -0.65 - -0.16, P<0.05).According to the treatment course grouping, the intervention for less than 3 months (SMD=-0.35, 95%CI: -0.66 - -0.03, P<0.05) and more than 3 months (SMD=-0.33, 95%CI: -0.62 - -0.03, P<0.05) showed significant therapeutic efficacy.Grouped by bacterial strains, the efficacy of a single microbial community was not significant (SMD=-0.16, 95%CI: -0.46 - 0.15, P>0.05), while the efficacy of a composite microbial community was significant (SMD=-0.51, 95%CI: -0.81 - -0.21, P<0.05). 【Conclusions】 Probiotic therapy is effective in improving the core symptoms of ASD patients, but is influenced by factors such as race, age and probiotic strain. Composite microbiota has better efficacy in Caucasian and underage populations.

Purpose: Li-Fraumeni syndrome (LFS) is a hereditary disorder caused by germline mutation in TP53. Owing to the rarity of LFS, data on its clinical features are limited. This study aimed to evaluate the clinical characteristics and prognosis of Korean patients with LFS. Materials and Methods: Patients who underwent genetic counseling and confirmed with germline TP53 mutation in the National Cancer Center in Korea between 2011 and 2022 were retrospectively reviewed. Data on family history with pedigree, types of mutation, clinical features, and prognosis were collected. Results: Fourteen patients with LFS were included in this study. The median age at diagnosis of the first tumor was 32 years. Missense and nonsense mutations were observed in 13 and one patients, respectively. The repeated mutations were p.Arg273His, p.Ala138Val, and pPro190Leu. The sister with breast cancer harbored the same mutation of p.Ala138Val. Seven patients had multiple primary cancers. Breast cancer was most frequently observed, and other types of tumor included sarcoma, thyroid cancer, pancreatic cancer, brain tumor, adrenocortical carcinoma, ovarian cancer, endometrial cancer, colon cancer, vaginal cancer, skin cancer, and leukemia. The median follow-up period was 51.5 months. Two and four patients showed local recurrence and distant metastasis, respectively. Two patients died of leukemia and pancreatic cancer 3 and 23 months after diagnosis, respectively. Conclusion This study provides information on different characteristics of patients with LFS, including types of mutation, types of cancer, and prognostic outcomes. For more appropriate management of these patients, proper genetic screening and multidisciplinary discussion are required.

Objective:To explore the cellular heterogeneity and the differences in branched trajectory of pericytes between keloids and localized scleroderma, and to provide new clues for the pathogenesis and therapeutic targets of the two skin fibrotic diseases.Methods:Single cell transcriptome sequencing (scRNA-seq) data of 3 cases of scleroderma, 4 cases of keloid and their corresponding 4 cases of adjacent normal skin samples were selected from GEO and GSA-Human databases, and the expression matrix of the data was drawn. Seurat 4.3.0 of R (4.2.2) was used to process the t-distributed stochastic neighbor embedding ( t-SNE) visualization map. Monocle 2.24.0 was used to analyze the pseudo-temporal trajectory of pericytes. Results:The unsupervised clustering of keloid and scleroderma skin tissues revealed 19 different cell populations, among which C7 and C11 cells were pericytes, marked by high expression levels of PDGFRB and RGS5 genes, accounting for 7.53% of the total cells. Pericytes can be further divided into 8 subgroups. Pseudo-temporal analysis revealed a branched trajectory with two major branches, that is, cell fate 1 and cell fate 2, which could be further divided into 5 cellular states of pericytes (S1-S5). S4 constituted the most of the prebranch, which represented the cellular state of the initial pericyte phenotype. S5 constituted the most of the cell fate 1 branch, which represented the early differentiation state of the pericyte phenotype. S1, S2, S3 constituted the most of the cell fate 2 branch. S3 represented the intermediate differentiation state of the pericyte phenotype, while S1 and S2 represented the terminal differentiation states of the pericyte phenotype. Compared with the uniform distribution of various differentiation states of pericytes in normal skin, the keloid pericytes mainly distributed in the prebranch (S4), cell fate 1 (S5) and the first half of cell fate 2 (S3), representing cellular states of the initial, early and intermediate phases of the pericyte phenotype. Branched expression analysis modeling revealed the overexpression of SOX4, COL4A1, COL6A3, AHR, CXCL3 and IL1R1 genes, et cetera. On the other hand, the localized scleroderma pericytes mainly distributed in the bottom half of cell fate 2 (S1, S2), representing the final differentiated phase of pericyte phenotype, which overexpressed ACTA2 and MYH11 genes.Conclusion:Pericytes in keloid and scleroderma are heterogenous and have different differentiation trajectories. Pericytes in keloid have stem-like characteristics, and play an important role in the pathologic characteristics of invasiveness and recurrence through high expression of genes related to cell stemness, epithelial-mesenchymal transition, invasiveness, and immune microenvironment regulation. However, pericytes in localized scleroderma may mainly transdifferentiate into myofibroblasts, leading to their fibrotic pathological phenotype.

Objective:To explore the cellular heterogeneity and the differences in branched trajectory of pericytes between keloids and localized scleroderma, and to provide new clues for the pathogenesis and therapeutic targets of the two skin fibrotic diseases.Methods:Single cell transcriptome sequencing (scRNA-seq) data of 3 cases of scleroderma, 4 cases of keloid and their corresponding 4 cases of adjacent normal skin samples were selected from GEO and GSA-Human databases, and the expression matrix of the data was drawn. Seurat 4.3.0 of R (4.2.2) was used to process the t-distributed stochastic neighbor embedding ( t-SNE) visualization map. Monocle 2.24.0 was used to analyze the pseudo-temporal trajectory of pericytes. Results:The unsupervised clustering of keloid and scleroderma skin tissues revealed 19 different cell populations, among which C7 and C11 cells were pericytes, marked by high expression levels of PDGFRB and RGS5 genes, accounting for 7.53% of the total cells. Pericytes can be further divided into 8 subgroups. Pseudo-temporal analysis revealed a branched trajectory with two major branches, that is, cell fate 1 and cell fate 2, which could be further divided into 5 cellular states of pericytes (S1-S5). S4 constituted the most of the prebranch, which represented the cellular state of the initial pericyte phenotype. S5 constituted the most of the cell fate 1 branch, which represented the early differentiation state of the pericyte phenotype. S1, S2, S3 constituted the most of the cell fate 2 branch. S3 represented the intermediate differentiation state of the pericyte phenotype, while S1 and S2 represented the terminal differentiation states of the pericyte phenotype. Compared with the uniform distribution of various differentiation states of pericytes in normal skin, the keloid pericytes mainly distributed in the prebranch (S4), cell fate 1 (S5) and the first half of cell fate 2 (S3), representing cellular states of the initial, early and intermediate phases of the pericyte phenotype. Branched expression analysis modeling revealed the overexpression of SOX4, COL4A1, COL6A3, AHR, CXCL3 and IL1R1 genes, et cetera. On the other hand, the localized scleroderma pericytes mainly distributed in the bottom half of cell fate 2 (S1, S2), representing the final differentiated phase of pericyte phenotype, which overexpressed ACTA2 and MYH11 genes.Conclusion:Pericytes in keloid and scleroderma are heterogenous and have different differentiation trajectories. Pericytes in keloid have stem-like characteristics, and play an important role in the pathologic characteristics of invasiveness and recurrence through high expression of genes related to cell stemness, epithelial-mesenchymal transition, invasiveness, and immune microenvironment regulation. However, pericytes in localized scleroderma may mainly transdifferentiate into myofibroblasts, leading to their fibrotic pathological phenotype.

Platinum-based chemotherapy resistance is a key factor of poor prognosis and recurrence in hepatocellular carcinoma (HCC). Herein, RNAseq analysis revealed that elevated tubulin folding cofactor E (TBCE) expression is associated with platinum-based chemotherapy resistance. High expression of TBCE contributes to worse prognoses and earlier recurrence among liver cancer patients. Mechanistically, TBCE silencing significantly affects cytoskeleton rearrangement, which in turn increases cisplatin-induced cycle arrest and apoptosis. To develop these findings into potential therapeutic drugs, endosomal pH-responsive nanoparticles (NPs) were developed to simultaneously encapsulate TBCE siRNA and cisplatin (DDP) to reverse this phenomena. NPs (siTBCE + DDP) concurrently silenced TBCE expression, increased cell sensitivity to platinum treatment, and subsequently resulted in superior anti-tumor effects both in vitro and in vivo in orthotopic and patient-derived xenograft (PDX) models. Taken together, NP-mediated delivery and the co-treatment of siTBCE + DDP proved to be effective in reversing chemotherapy resistance of DDP in multiple tumor models.

ABSTARCT Purpose To investigate the clinicopathologic characteristics and genetic mutations of metastatic follicular thy-roid carcinoma(FTC).Methods A total of 22 cases of meta-static FTC were collected,including previous medical history,imaging,treatments and outcomes,and next-generation sequen-cing study and Sanger sequencing were performed in 12 cases.Results There were 16 women and 6 men.Sixteen cases were older than 50 years.Seven cases presented with metastases as the first symptom.Fourteen cases developed metastases 3 to 12 years after thyroid surgery.Sixteen cases developed bone metas-tasis,10 cases had lung metastasis,and 3 cases had brain me-tastasis.Those patients with multiple bone metastases progressed during the follow-up period.The common gene mutations in me-tastases were NRAS p.Q61R(6 cases),HRAS p.Q61R(2 ca-ses)and KRAS p.Q61R(1 case),followed by TERT promoter mutation(8 cases).Other mutated genes included KEL,BRCA1/2,ALK,ROS1,ErbB4,etc.Conclusion FTC has a high misdiagnosis rate.Those diagnosed with FTC should under-go regular systemic examinations to detect potential metastasis,especially in bone,lung,and brain.Further research on the sig-nificance of NRAS and other molecular indicators in FTC metas-tasis will help to better predict its biological behaviors.