Tumors exhibit abnormal glucose metabolism, consuming excessive glucose and excreting lactate, which constructs a tumor microenvironment that facilitates cancer progression and disrupts immunotherapeutic efficacy. Currently, tumor glucose metabolic dysregulation to reshape the immunosuppressive microenvironment and enhance immunotherapy efficacy is emerging as an innovative therapeutic strategy. However, glucose metabolism modulators lack specificity and still face significant challenges in overcoming tumor delivery barriers, microenvironmental complexity, and metabolic heterogeneity, resulting in poor clinical benefit. Nanomedicines, with their ability to selectively target tumors or immune cells, respond to the tumor microenvironment, co-deliver multiple drugs, and facilitate combinatorial therapies, hold significant promise for enhancing immunotherapy through tumor glucose metabolic reprogramming. This review explores the complex interactions between tumor glucose metabolism-specifically metabolite transport, glycolysis processes, and lactate-and the immune microenvironment. We summarize how nanomedicine-mediated reprogramming of tumor glucose metabolism can enhance immunotherapy efficacy and outline the prospects and challenges in this field.

Objective: To systematically evaluate the influencing factors for medication compliance in patients with comorbidities of chronic diseases, so as to provide the evidence for improving medication compliance. Methods: Literature on influencing factors for medication compliance in patients with comorbidities of chronic diseases were retrived from CNKI, Wanfang Data, VIP, SinoMed, PubMed, Web of Science, Cochrane Library and Embase from inception to January 20, 2024. After independent literature screening, data extraction, and quality assessment by two researchers, a meta-analysis was performed using RevMan 5.4 and Stata 16.0 softwares. Literature were excluded one by one for sensitivity analysis. Publication bias was assessed using Egger's test. Results: Initially, 7 365 relevant articles were retrieved, and 35 of them were finally included, with a total sample size of about 150 000 individuals. There were 30 cross-sectional studies and 5 cohort studies; and 11 high-quality studies and 24 medium-quality studies. The meta-analysis showed that the demographic factors of lower level of education (OR=2.148, 95%CI: 1.711-2.696), lower economic income (OR=1.897, 95%CI: 1.589-2.264), male (OR=0.877, 95%CI: 0.782-0.985), living alone (OR=2.833, 95%CI: 1.756-4.569) and unmarried (OR=2.784, 95%CI: 1.251-6.196); the medication treatment factors of polypharmacy (OR=1.794, 95%CI: 1.190-2.706), potentially inappropriate medication (OR=2.988, 95%CI: 1.527-5.847), low frequency of daily medication (OR=0.533, 95%CI: 0.376-0.754) and adverse drug reactions (OR=3.319, 95%CI: 1.967-5.602); the disease factors of long course of disease (OR=2.118, 95%CI: 1.643-2.730), more comorbidities (OR=1.667, 95%CI: 1.143-2.431) and cognitive impairment (OR=2.007, 95%CI: 1.401-2.874); and the psychosocial factors of poor belief in taking medication (OR=1.251, 95%CI: 1.011-1.547), poor self-rated health (OR=1.990, 95%CI: 1.571-2.522) and being guided by healthcare professionals (OR=0.151, 95%CI: 0.062-0.368) were the influencing factors for medication compliance in patients with chronic comorbidities. Conclusion The medication compliance in patients with comorbidities of chronic diseases is associated with demographic factors, pharmacological factors, disease factors and psychosocial factors, mainly including living alone, adverse drug reactions, course of disease, number of comorbidities and medication beliefs.

Objective:To analyze the role of dandelion and mulberry leaf in the progression of acute myeloid leukemia(AML)by network pharmacology,and to clarify the active components and their mechanisms in treating AML.Methods:The active components of dandelion and mulberry leaf were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).The targets were predicted by SwissTargetPrediction Database.The AML-related genes and protein targets were retrieved from the SymMap Database,the GeneCards Human Gene Database,the DisGeNET Database,and the Online Mendelian Inheritance in Man(OMIM)Database.The AML-related genes and target genes of dandelion and mulberry leaf were compared by comparative analysis and were identify by the enrichment genes,followed by Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis.The drug-active component-target network and protein-protein interaction(PPI)network were constructed by Cytoscape 3.8.0 software,and the core genes were selected by CytoNCA plugin;the molecular docking was conducted by AutoDock software.Results:After filtering by databases,39 active components were identified,and 148 common targets between dandelion-mulberry leaf and AML were collected.The GO functional enrichment analysis mainly involved cytokine-mediated signaling pathways,positive regulation of kinase activity,and oxidative stress responses.The KEGG signaling pathway enrichment analysis focused on the phosphatidylinositol 3 kinase/protein kinase B(PI3K-AKT)signaling pathway,the tumor necrosis factor(TNF)signaling pathway,and the Janus kinase/signal transducer and activator of transcription(JAK-STAT)signaling pathway.The key targets were identified by topological analysis including signal transducer and activator of transcription 3(STAT3),epidermal growth factor receptor(EGFR),protein kinase B1(AKT1),recombinant human epidermal growth factor(EGF),vascular endothelial growth factor A(VEGFA),oncogene MYC,tumor protein P53(TP53),mitogen-activated protein kinase 3(MAPK3),cysteiny asparate specific protease-3(CASP3),oncogene SRC,heat shock protein 90 alpha family class A member 1(HSP90AA1),tenascin XB1(CTNNB1),phosphoinositide kinase-3 catalytic subunit alpha(PIK3CA),interleukin 6(IL-6),TNF,mitogen-activated protein kinase 1(MAPK1),and phosphatidylinositide kinase-3 regulatory subunit 1(PIK3R1).The molecular docking results showed the highest affinity pairing to be taraxerol with MYC(-8.74 kcal·mol-1),and quercetin,kaempferol,luteolin,and artemetin demonstrated good binding affinities with various targets.Conclusion:The main active components of dandelion-mulberry leaf,such as quercetin,taraxerol,kaempferol,luteolin,and artemetin,may exert the anti-AML effect by regulating AKT1,STAT3,HSP90AA1,IL-6,and MAPK1;regulation the PI3K-AKT signaling pathway may be the critical mechanism of anti-AML effect by dandelion-mulberry leaf.

Objective:To compare the effectiveness of two types of robotic training in improving the lower extremity motor functioning of children with spastic cerebral palsy (SCP).Methods:Twenty-eight children with SCP were randomly divided into a control group and an experimental group, each of 14. Both groups received conventional exercise therapy, paraffin therapy, neuromuscular electrical stimulation, and massage. Both also performed 30 minutes of gait training five days a week for eight weeks assisted by either a Lokomat or a Relink lower limb rehabilitation robot. Before and after the treatment, both groups were evaluated using the Gross Motor Function Measure (GMFM), the Pediatric Balance Scale (PBS), the Modified Tardieu Scale (MTS), the six-minute walk test (6MWT), the Physiological Cost Index (PCI) and their self-selected walking speed (SWS).Results:Significant improvement in all of the measurements were observed in both groups. After the treatment, there were no significant differences between the two group in the average GMFM (section D and E) or PBS scores. The average MTS R1 and R2, SWS, 6MWT and PCI results of the experimental group were, however, significantly better than those of the control group.Conclusion:Applying either the Lokomat or Relink robot in lower extremity rehabilitation improves the lower extremity motor function of children with grade II-III SCP. The Relink robot is the more effective in improving triceps surae spasm and walking ability.

Objective:To summarize the best evidence of medication adherence interventions for patients with multiple chronic conditions.Methods:According to the "6S" evidence model, literature on medication adherence in patients with multiple chronic conditions was retrieved from BMJ Best Clinical Practice, UpToDate, Medlive, National Institute for Health and Clinical Excellence, Cochrane Library, Embase, PubMed, Web of Science, China Biology Medicine disc, China National Knowledge Infrastructure, WanFang data and so on. The search period was from establishing the database to August 30, 2023.Results:A total of 16 articles were included, including three guidelines, four expert consensus, seven systematic reviews, and two meta-analyses. Twenty-seven pieces of evidence were summarized from six aspects of compliance assessment, educational intervention, behavioral intervention, optimized treatment program, technical reminder intervention, and social-psychological-emotional intervention.Conclusions:The best evidence of medication adherence interventions for patients with multiple chronic conditions summarized provides a reference for medical and nursing staff to develop medication adherence interventions.

Objective:Investigate the potential of diosmin(DSM)in alleviating anxiety behavior associated with post-traumatic stress disorder(PTSD)in mice.Methods:A PTSD-like mouse model was induced with continuous restraint,forced swimming,anesthesia,and electric shock.DSM was administered via intraperitoneal injection.The impact of DSM on anxiety behavior was assessed using open-field and elevated maze tests.Databases such as Swiss Tar-get Prediction,Drug Bank,TTD,and Gene Cards were utilized to gather the pertinent targets associated with DSM and PTSD.The Venny2.1 tool was employed to identify overlapping targets between DSM components and those relevant to PTSD.A protein-protein interaction(PPI)network was constructed and topological analysis was conducted to identify core targets.The core targets were further analyzed through GO classification and KEGG pathway enrichment.The"component-disease-target-pathway"network of DSM anti-PTSD was constructed.Immunofluorescence staining of mouse brain tissue was used to verify the core targets.Results:DSM significantly alleviates anxiety-like behavior in PTSD-like mice.The result of network pharmacology revealed 53 common targets,15 key targets,649 biological proces-ses,and 46 differential signaling pathways of DSM in the treatment of PTSD.Key targets CCL5,JNK,and TNF-α with relatively high screening values were used for immunofluorescence staining of mouse brain slices.The expression of CCL5,JNK,and TNF-α were highly higher in the PTSD group than the normal group,and DSM could significantly in-hibit their expression in PTSD-Like mice.Conclusion:DSM can significantly alleviate anxiety-like behaviors in PTSD-like mice,and its mechanism of action may be closely related to the inhibition of inflammatory immune response.

OBJECTIVE: To explore the genetic basis for a child with Neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities (NEDASB). METHODS: A child with NEDASB who presented at the Third Affiliated Hospital of Zhengzhou University in July 2021 was selected as the subject. Peripheral blood samples of the child and her parents were collected and subjected to high-throughput sequencing. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child was found to harbor a heterozygous c.820_828delinsCTTCA (p.Thr274Leufs*121) variant of the NOVA2 gene, for which both of her parents were of wild type. The variant was predicted as pathogenic based on the guidelines from the American College of Medical Genetics and Genomics. CONCLUSION The heterozygous c.820_828delinsCTTCA (p.Thr274Leufs*121) variant of the NOVA2 gene probably underlay the disease in this child. Above finding has enriched the spectrum of NOVA2 gene variants and provided a basis for genetic counseling and prenatal diagnosis for this family.
Child ; Female ; Humans ; Pregnancy ; Autistic Disorder/genetics* ; Brain ; Computational Biology ; Genetic Counseling ; Mutation ; Nerve Tissue Proteins/genetics* ; Neuro-Oncological Ventral Antigen ; Neurodevelopmental Disorders ; RNA-Binding Proteins

ObjectiveTo investigate the association between spontaneous portosystemic shunt （SPSS） and hepatorenal syndrome （HRS） in patients with liver cirrhosis. MethodsA retrospective analysis was performed for 93 patients with SPSS from Dezhou Hospital， Qilu Hospital of Shandong University， from January 2015 to January 2022， and the patients were followed up for 12 months with the onset of HRS as the observation endpoint. According to the presence or absence of HRS， the 93 patients with SPSS were divided into HRS group with 38 patients （40.86%） and non-HRS group with 55 patients （59.14%）， and the two groups were compared in terms of clinical data， laboratory data， complication， and shunt diameter. Based on the maximum shunt vein diameter of 1.5 cm， the 93 patients with SPSS were divided into high shunt group with 52 patients （55.91%） and low shunt group with 41 patients （44.09%）， and with the onset of HRS as the observation endpoint， the two groups were compared in terms of the incidence rate of HRS and survival time curve. The independent-samples t test was used for comparison of normally distributed continuous data with homogeneity of variance between two groups， and the chi-square test was used for comparison of categorical data between two groups. The receiver operating characteristic （ROC） curve was used to predict cut-off values， the Kaplan-Meier curve was used for comparison of survival time， and the Log-rank test was used to compare the differences in survival curves. The multivariate Cox regression analysis was used to investigate risk factors. ResultsCompared with the non-HRS group， the HRS group had significant increases in Child-Pugh score， Child-Pugh class， MELD score， serum creatinine， blood urea nitrogen， alanine aminotransferase， aspartate aminotransferase， maximum shunt vein diameter， the incidence rates of hepatic encephalopathy and spontaneous bacterial peritonitis， and the degree of ascites， as well as significant reductions in main portal vein diameter， serum sodium and albumin （all P<0.05）. Compared with the low shunt group， the high shunt group had a significant increase in the incidence rate of HRS （51.92% vs 26.83%， χ²=5.974， P=0.015） and a significant reduction in the time to the onset of HRS （Log-rank P=0.033）. A maximum shunt vein diameter of >1.5 cm （hazard ratio ［HR］=1.123， 95% confidence interval ［CI］： 1.041‍ ‍—‍ ‍1.211， P=0.003）， an increase in MELD score （HR=1.205， 95%CI： 1.076‍ ‍—‍ ‍1.437， P=0.039）， a reduction in serum albumin （HR=0.890， 95%CI： 0.814‍ ‍—‍ ‍0.974， P=0.011）， an increase in the degree of ascites （HR=2.099， 95%CI： 1.066‍ ‍—‍ ‍4.130， P=0.032）， and spontaneous bacterial peritonitis （HR=2.259， 95%CI： 1.020‍ ‍—‍ ‍5.003， P=0.045） were independent risk factors for the onset of HRS in SPSS patients. ConclusionThere is an association between SPSS and HRS， and shunt diameter >1.5 cm was an independent risk factor for HRS in SPSS patients， which should be taken seriously and require early intervention in clinical practice.

OBJECTIVE: To analyze the clinical phenotype and genetic characteristics of a child with Hereditary spastic paraplegia (HSP). METHODS: A child with HSP who was admitted to the Third Affiliated Hospital of Zhengzhou University on August 10, 2020 due to discovery of tiptoeing for 2 years was selected as the study subject, and relevant clinical data was collected. Peripheral blood samples of the child and her parents were collected for the extraction of genomic DNA. And trio-whole exome sequencing (trio-WES) was carried out. Candidate variants were verified by Sanger sequencing. Bioinformatic software was used to analyze the conservation of variant sites. RESULTS: The child was a 2-year-and-10-month-old female with clinical manifestations including increased muscle tone of lower limbs, pointed feet, and cognitive language delay. Trio-WES results showed that she had harbored compound heterozygous variants of c.865C>T (p.Gln289*) and c.1126G>A (p.Glu376Lys) of the CYP2U1 gene. And the corresponding amino acid for c.1126G>A (p.Glu376Lys) is highly conserved among various species. Based on guidelines from the American College of Medical Genetics and Genomics, the c.865C>T was predicted as a pathogenic variant (PVS1+PM2_Supporting), and c.1126G>A was rated as a variant of uncertain significance (PM2_Supporting+PM3+PP3). CONCLUSION The child was diagnosed with HSP type 56 due to compound variants of the CYP2U1 gene. Above findings have enriched the mutation spectrum of the CYP2U1 gene.
Female ; Humans ; Cytochrome P450 Family 2/genetics* ; Mutation ; Pedigree ; Phenotype ; Spastic Paraplegia, Hereditary/genetics* ; Infant

OBJECTIVE: To explore the genetic basis for a EAST/SeSAME syndrome child featuring epilepsy, ataxia, sensorineural deafness and intellectual disability. METHODS: A child with EAST/SeSAME syndrome who had presented at the Third Affiliated Hospital of Zhengzhou University in January 2021 was selected as the study object. Peripheral blood samples of the child and her parents were collected and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing. RESULTS: Genetic testing revealed that the child has harbored compound heterozygous variants of the KCNJ10 gene, namely c.557T>C (p.Val186Ala) and c.386T>A (p.Ile129Asn), which were inherited from her mother and father, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted as likely pathogenic (PM1+PM2_Supporting+PP3+PP4; PM1+PM2_Supporting+PM3+PP3+PP4). CONCLUSION The patient was diagnosed with EAST/SeSAME syndrome due to the compound heterozygous variants of the KCNJ10 gene.
Humans ; Child ; Female ; Intellectual Disability/genetics* ; Hearing Loss, Sensorineural/genetics* ; Ataxia ; Genetic Diseases, X-Linked ; Mutation