ObjectiveTo investigate the chemical constituents of Chuanxiong Rhizoma-Paeoniae Radix Rubra（CRPRR） that cross the blood-brain barrier in rats with ischemic stroke， their brain-protective effects， and their impact on inflammatory factors including tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-18 （IL-18） based on ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS） and pharmacodynamic experiments. MethodsA focal cerebral ischemia-reperfusion injury model was established in rats via the middle cerebral artery occlusion/reperfusion （MCAO/R） method using intraluminal suture. Neurological function was evaluated using behavioral scoring. UPLC-Q-TOF-MS was employed to identify the chemical constituents of CRPRR that crossed the blood-brain barrier and entered the cerebrospinal fluid in MCAO/R model rats. Male Sprague-Dawley rats were randomly divided into six groups： sham operation group， model group， low-， medium-， and high-dose CRPRR groups （1.35， 2.7， 5.4 g·kg^-1， respectively）， and an edaravone group （5 mg·kg^-1）， with 12 rats in each group. The sham and model groups received normal saline， while the treatment groups received the respective doses of CRPRR once daily by gavage for three consecutive weeks. The brain-protective effects of CRPRR were assessed using the Longa five-point scoring method， open field test， Morris water maze， 2，3，5-triphenyltetrazolium chloride （TTC） staining， hematoxylin and eosin （HE） staining， and transmission electron microscopy. ResultsNine chemical constituents were identified in the cerebrospinal fluid containing CRPRR， namely paeoniflorin， senkyunolide F， senkyunolide G， paeonimetabolin Ⅰ， paeoniflorin derivative， senkyunolide H， benzoylpaeoniflorin， senkyunolide A， and ligustilide. Animal experiment results showed that compared with the sham operation group， the model group exhibited disordered neuronal arrangement， severe vacuolation， nuclear pyknosis， and evident mitochondrial swelling. Chromatin aggregation and peripheralization were also observed. Neurological scores and the number of crossings in the central region were significantly increased （P<0.01）， while platform crossings were significantly decreased （P<0.01）， and clear infarct areas were present （P<0.01）. Serum levels and protein expression of TNF-α， IL-1β， and IL-18 were significantly elevated （P<0.01）. Compared with the model group， all dose groups of CRPRR showed marked improvement in neuronal morphology which was close to the normal level， with mitochondrial swelling alleviated and chromatin distribution more uniform. The medium- and high-dose groups significantly reduced neurological scores （P<0.01）， while the low-， medium-， and high-dose groups significantly reduced the number of central crossings （P<0.01） and infarct volume （P<0.01）， and decreased TNF-α， IL-1β， and IL-18 levels （P<0.05， P<0.01） compared with the model group. Furthermore， the medium- and high-dose groups significantly reduced TNF-α protein expression （P<0.05，P<0.01）， and the high-dose group significantly reduced IL-1β and IL-18 protein expression （P<0.01）. ConclusionThis study confirmed that CRPRR improves neurological function and alleviates brain tissue damage in MCAO/R rats. Its mechanism may be associated with the downregulation of inflammatory factors TNF-α， IL-1β， and IL-18， as well as the presence of nine active chemical constituents in cerebrospinal fluid， namely paeoniflorin， senkyunolide F， senkyunolide G， paeonimetabolin Ⅰ， paeoniflorin derivative， senkyunolide H， benzoylpaeoniflorin， senkyunolide A， and ligustilide， which are closely related to their brain-protective effects.

ObjectiveTo investigate the chemical constituents of Chuanxiong Rhizoma-Paeoniae Radix Rubra（CRPRR） that cross the blood-brain barrier in rats with ischemic stroke， their brain-protective effects， and their impact on inflammatory factors including tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-18 （IL-18） based on ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS） and pharmacodynamic experiments. MethodsA focal cerebral ischemia-reperfusion injury model was established in rats via the middle cerebral artery occlusion/reperfusion （MCAO/R） method using intraluminal suture. Neurological function was evaluated using behavioral scoring. UPLC-Q-TOF-MS was employed to identify the chemical constituents of CRPRR that crossed the blood-brain barrier and entered the cerebrospinal fluid in MCAO/R model rats. Male Sprague-Dawley rats were randomly divided into six groups： sham operation group， model group， low-， medium-， and high-dose CRPRR groups （1.35， 2.7， 5.4 g·kg^-1， respectively）， and an edaravone group （5 mg·kg^-1）， with 12 rats in each group. The sham and model groups received normal saline， while the treatment groups received the respective doses of CRPRR once daily by gavage for three consecutive weeks. The brain-protective effects of CRPRR were assessed using the Longa five-point scoring method， open field test， Morris water maze， 2，3，5-triphenyltetrazolium chloride （TTC） staining， hematoxylin and eosin （HE） staining， and transmission electron microscopy. ResultsNine chemical constituents were identified in the cerebrospinal fluid containing CRPRR， namely paeoniflorin， senkyunolide F， senkyunolide G， paeonimetabolin Ⅰ， paeoniflorin derivative， senkyunolide H， benzoylpaeoniflorin， senkyunolide A， and ligustilide. Animal experiment results showed that compared with the sham operation group， the model group exhibited disordered neuronal arrangement， severe vacuolation， nuclear pyknosis， and evident mitochondrial swelling. Chromatin aggregation and peripheralization were also observed. Neurological scores and the number of crossings in the central region were significantly increased （P<0.01）， while platform crossings were significantly decreased （P<0.01）， and clear infarct areas were present （P<0.01）. Serum levels and protein expression of TNF-α， IL-1β， and IL-18 were significantly elevated （P<0.01）. Compared with the model group， all dose groups of CRPRR showed marked improvement in neuronal morphology which was close to the normal level， with mitochondrial swelling alleviated and chromatin distribution more uniform. The medium- and high-dose groups significantly reduced neurological scores （P<0.01）， while the low-， medium-， and high-dose groups significantly reduced the number of central crossings （P<0.01） and infarct volume （P<0.01）， and decreased TNF-α， IL-1β， and IL-18 levels （P<0.05， P<0.01） compared with the model group. Furthermore， the medium- and high-dose groups significantly reduced TNF-α protein expression （P<0.05，P<0.01）， and the high-dose group significantly reduced IL-1β and IL-18 protein expression （P<0.01）. ConclusionThis study confirmed that CRPRR improves neurological function and alleviates brain tissue damage in MCAO/R rats. Its mechanism may be associated with the downregulation of inflammatory factors TNF-α， IL-1β， and IL-18， as well as the presence of nine active chemical constituents in cerebrospinal fluid， namely paeoniflorin， senkyunolide F， senkyunolide G， paeonimetabolin Ⅰ， paeoniflorin derivative， senkyunolide H， benzoylpaeoniflorin， senkyunolide A， and ligustilide， which are closely related to their brain-protective effects.

Breast milk is the optimal natural food for newborns. However， some newborns cannot receive maternal breast milk due to reasons such as mother-infant separation or insufficient lactation. The establishment of human milk banks （HMB） can effectively address these issues， thereby increasing the breastfeeding rate among hospitalized newborns and improving their quality of survival. However， HMB in China is still in the development and improvement stage. Its implementation involves a series of ethical issues， such as informed consent， privacy protection， economic incentives， quality and safety， and fair resource distribution， which hinder HMB’s widespread promotion. Therefore， discussing the ethical dilemmas faced by the widespread establishment of HMB in China’s hospitals and analyzing coping strategies are crucial for improving the breastfeeding rate of newborns. This paper deeply analyzed and sorted out the ethical issues and challenges currently faced by HMB in China， and proposed corresponding strategies， including “ensuring informed consent and voluntary participation of both donors and recipients，” “protecting the privacy of donors and recipients，” “establishing an ethics-based moral incentive and social support system，” “strictly controlling quality and safety issues”， and “developing fair and rational policies，” aiming to provide a reference solution for addressing ethical concerns in the establishment and operation of HMB.

Synthetic biology is a crucial tool for the development of the bio-industry and bio-economy, representing a significant aspect of new quality productive forces. As a core course for graduate students in bioengineering, Synthetic Biology plays a vital role in ensuring the supply of essential talents for the development of the bio-industry in the new era. To better serve regional economic development and provide high-level talents for China's progress in the bio-industry, we analyzed typical issues encountered in the past teaching activities, set up a multi-disciplinary teaching team, optimized the course contents, adjusted the teaching mode, and mobilized students' learning interest. With the application of scientific research project as the starting point, we guided students to think and discuss deeply through the simulation of application writing and project defense, which improved students' critical thinking and innovative thinking. With industrialization as a focus, we explored a new training model combining production, education, and research through the joint practice base of the university and enterprises introduced typical cases of biomanufacturing to encourage students to engage in scientific research. The teaching reform significantly enhances the comprehensive abilities and national sentiments of graduate students. This paper hopes to serve as a reference for colleagues engaged in teaching in this field.
Synthetic Biology/education* ; Teaching ; China ; Humans

Objective:To investigated the safety and efficacy of donor-derived CD19+ or sequential CD19+ CD22+ chimeric antigen receptor T-cell (CAR-T) therapy in patients with B-cell acute lymphoblastic leukemia (B-ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:The data of 22 patients with B-ALL who relapsed after allo-HSCT and who underwent donor-derived CAR-T therapy at the Zhujiang Hospital of Southern Medical University and the 920th Hospital of Joint Logistics Support Force of the People’s Liberation Army of China from September 2015 to December 2022 were retrospectively analyzed. The primary endpoint was overall survival (OS), and the secondary endpoints were event-free survival (EFS), complete remission (CR) rate, and Grade 3-4 adverse events.Results:A total of 81.82% ( n=18) of the 22 patients achieved minimal residual disease-negative CR after CAR-T infusion. The median follow-up time was 1037 (95% CI 546–1509) days, and the median OS and EFS were 287 (95% CI 132-441) days and 212 (95% CI 120-303) days, respectively. The 6-month OS and EFS rates were 67.90% (95% CI 48.30%-84.50%) and 58.70% (95% CI 37.92%-79.48%), respectively, and the 1-year OS and EFS rates were 41.10% (95% CI 19.15%-63.05%) and 34.30% (95% CI 13.92%-54.68%), respectively. Grade 1-2 cytokine release syndrome occurred in 36.36% ( n=8) of the patients, and grade 3-4 occurred in 13.64% of the patients ( n=3). Grade 2 and 4 graft-versus-host disease occurred in two patients. Conclusion:Donor-derived CAR-T therapy is safe and effective in patients with relapsed B-ALL after allo-HSCT.

POEMS syndrome is a rare plasma cell dysplasia. Its clinical manifestations include polyneuropathy, monoclonal protein, increased extravascular volume load, endocrinopathy, organomegaly and skin changes. The complex and atypical symptoms at presentation make early diagnosis challenging due to multiple system involvement. Peripheral neuropathy, limb numbness, is the most common initial symptom of this disease. However, case reports of increased extravascular volume load are rare. This article collected and analyzed the clinical data of two groups of patients with different initial symptoms (increased extravascular volume load and limb numbness). The clinical characteristics and treatment responses were summarized.

Objective:To screen the differentially expressed immune-related genes(DEIRGs)in in-stent restenosis(ISR),and to analyze the immune cell infiltration in ISR,and to clarify the mechanism of occurrence and development of ISR.Methods:The mRNA gene expression data of GSE46560 dataset samples were downloaded from the Gene Expression Omnibus(GEO),and divided into ISR group and non-ISR group.The"Limma"package in R software was used to identify the differentially expressed genes(DEGs)which were then intersected with immune-related genes(IRGs)to identify the DEIRGs in ISR;R software was used for Gene Ontology(GO)functional enrichment andalysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis on DEIRGs;the STRING database was used to construct the protein-protein interaction(PPI)network,which was visualized and analyzed for Hub genes by Cytoscape software;the receiver operating characteristic(ROC)curve of the Hub genes were plotted,and the area under the curve(AUC)was calculated and the diagnostic value was evaluated;CIBERSORT software was used to analyze the immune cell infiltration in ISR;Pearson correlation analysis was used to analyze the relationships between the immune cells and the relationships between the immune cells and key genes.Results:A total of 331 DEGs were identified(P<0.05,|log2FC|>1),including 176 upregulated genes and 155 downregulated genes,and 38 DEIRGs were obstained.The GO functional enrichment analysis results showed that the DEIRGs were mainly enriched in biological processes(BP)such as defense response,immune response,and immune system;in cellular components(CC),the DEIRGs were located primarily in the extracellular region and cytoplasmic membrane;and in molecular functions(MF),the DEIRGs were mainly involved in regulating signaling receptor binding and cytokine receptor activity.The KEGG signaling pathway enrichment analysis results indicated that the DEIRGs in ISR were primarily enriched in the phosphatidylinositol 3-kinase/protein kinase B(PI3K-AKT)and transforming growth factor-β(TGF-β)signaling pathways.In the PPI network,CD19 had the highest node among the top 10 Hub genes.Compared with non-ISR group,the expression level of the CD19 gene in the samples in ISR group was increased(P<0.05).The AUC value in the ROC curve of CD19 gene expression was 0.92(P<0.05).The immune cell infiltration analysis results showed that compared with non-ISR group,the infiltration level of T lymphocyte follicular helper(Tfh)cells in the patients in ISR group were increased(P<0.05),the infiltration levels of immature B lymphocytes,CD8+T lymphocytes,naive CD4+T lymphocytes,and M0 macrophages were increased,but the differences were not statistically significant(P>0.05),while the infiltration levels of memory B lymphocytes,activated memory CD4+T lymphocytes,regulatory T cells,resting natural killer(NK)cells,activated NK cells,monocytes,resting mast cells,and neutrophils were decreased,but the differences were not statistically significant(P>0.05).There were positive correlations between Tfh cells and M0 macrophages and resting mast cells(r=0.88,P<0.05;r=0.68,P<0.05),and there were negative correlations between Tfh cells and monocytes and neutrophils(r=-0.49,P<0.05;r=-0.42,P<0.05).Conclusion:CD19 may influence the occurrence and development of ISR by regulating the activation of the PI3K-AKT signaling pathway to affect the Tfh and B lymphocytes.CD19 can serve as a biomarker for the diagnosis of ISR.

Objective To investigate the clinical features in children with invasive pneumococcal disease (IPD) and early warning indicators of severe case.Methods The case data of 101 children inpatients with IPD isolated Streptococcus pneumoniae (Sp) at least once blood culture in this hospital from January 2007 to De-cember 2021 were collected retrospectively.The children patients were divided into the pediatric intensive care unit (PICU) group (35 cases) and general ward group (66 cases) according to whether or not entering PICU during hospitalization.The general clinical data,infection types and results of drug sensitivity test and bacteri-al strain serotype identification were compared between the two groups and analyzed.Results Compared with the general ward group,the male proportion,proportions of complicating nervous system disease and iron-defi-ciency anemia,winter incidence rate,disturbance of consciousness,convulsion,dyspnea,heart rate increase,oc-currence rate of vomiting and diarrhea,proportion of peripheral blood neutrophilic granulocytes,C reactive protein (CRP),lactic dehydrogenase (LDH) level,Hb<90 g/L,LDH>700 U/L,creatine kinase isoenzyme-MB (CK-MB) abnomality,proportions of bacterial meningitis,sepsis and severe pneumonia in the PICU group were higher,the proportion of 3-97 percentile of body weight,bronchopneumonia and no-focus blood stream infection were lower,WBC,Hb and albumin level were lower,and the differences were statistically significant (P<0.05).Eleven kinds of serotypes were identified in this study,ranking the top five in order were 6B,14,19F,23F and 19A.Pneumococcal 13-valent conjugate vaccine (PCV13) could cover 96.9％ of the IPD sero-types.The multivariate logistic regression analysis showed that consciousness disturbance,convulsion,per-centage of neutrophils increase,Hb<90 g/L,LDH>700 U/L and CK-MB abnormality indicated the condition of IPD children patients was critical,which was the early-warning indicator of entering PICU (P<0.05).Con-clusion Severe IPD lacks the early specific early-warning indicator,and the cover rate of PCV13 is high.

Objective:To investigate key differential expressed genes(DEGs),enriched biological functions and signaling pathways in exosomes derived from angiosarcoma cells ISOHAS and angiosarcoma stem-like cells Sphere by bioinformatics analysis,to provide new therapeutic targets for angiosarcoma.Methods:Transcriptome sequencing of exosomes derived from ISOHAS and Sphere were performed to screen for DEGs by|log2FC|>2 and FDR<0.05 as criteria.Bioinformatics analysis was used to enrich GO and KEGG pathways of DEGs to identify biological functions and signaling pathways of enriched DEGs.STRING database was used to screen key DEGs,and iPath was used to visualize to identify metabolic pathways enriched by DEGs.Results:Transcriptome sequencing results showed that 91 DEGs were identified in exosomes derived from ISOHAS and Sphere.GO and KEGG pathway enrichment analysis demonstrated that main biological functions and signaling pathways enriched by DEGs were response to glucocorticoid and TNF signaling pathway,respectively.STRING database demonstrated that TNF and IL-6 were key DEGs.iPath metabolic network analysis demonstrated that DEGs were mainly identified in lipid metabolism and nucleotide metabolism.Conclusion:Sphere-derived exosomes may influence occurrence and development of angiosarcoma by carrying key genes TNF and IL-6 to interfere with glucocorticoid response,TNF signaling pathway,lipid metabolism,nucleotide metabolism and other biological functions and signaling pathways,providing new ideas for therapeutic targets for angiosarcoma.