Glioma represents the most prevalent malignant tumor of the central nervous system, with chemotherapy serving as an essential adjunctive treatment. However, most chemotherapeutic agents exhibit limited ability to penetrate the blood-brain barrier (BBB). This study introduced a novel dual-targeting strategy for glioma therapy by modulating the formation of nanobody-driven protein coronas to enhance the brain and tumor-targeting efficiency of hydrophobic cisplatin prodrug-loaded lipid nanoparticles (C8Pt-Ls). Specifically, nanobodies (Nbs) with fibrinogen-binding capabilities were conjugated to the surface of C8Pt-Ls, resulting in the generation of Nb-C8Pt-Ls. Within the bloodstream, Nb-C8Pt-Ls could bound more fibrinogen, forming the protein corona that specifically interacted with LRP-1, a receptor highly expressed on the BBB. This interaction enabled a "Hitchhiking Effect" mechanism, facilitating efficient trans-BBB transport and promoting effective brain targeting. Additionally, the protein corona interacted with LRP-1, which is also overexpressed in glioma cells, achieving precise tumor targeting. Computational simulations and SPR detection clarified the molecular interaction mechanism of the Nb-fibrinogen-(LRP-1) complex, confirming its binding specificity and stability. Our results demonstrated that this strategy significantly enhanced C8Pt accumulation in brain tissues and tumors, induced apoptosis in glioma cells, and improved therapeutic efficacy. This study provides a novel framework for glioma therapy and underscores the potential of protein corona modulation-based dual-targeting strategies in advancing treatments for brain tumors.

In recent years， significant progress has been made in the standardized diagnosis and treatment of pancreatic cancer in China. From the lack of treatment options and poor drug efficacy at the beginning to the current comprehensive treatment modality integrating surgery， chemotherapy， radiotherapy， immunotherapy， and targeted therapy under multidisciplinary decision-making， the diagnosis and treatment of pancreatic cancer has gradually achieved higher levels of individualization， refinement， and precision. With reference to the latest evidence-based medical data， this article discusses the hot topics in the diagnosis and treatment of pancreatic cancer and explores the future development directions of this field.

UNLABELLED: OBJECTIVE：To explore the clinical characteristics and genetic etiology of a child with CAKUTHED syndrome. METHODS: A child who was admitted to the neonatal department of Gansu Provincial Maternal and Child Health Care Hospital due to "neonatal asphyxia" in May 2021 was selected as the study subject. Genomic DNA was extracted from peripheral venous blood samples from the child and his parents, and whole exome sequencing (WES) was carried out. Sanger sequencing was used to verify the candidate variant of the PBX1 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of candidate variants was rated. This study was approved by the Medical Ethics Committee of the Hospital [Ethics No.: 2021GSFY (65)]. RESULTS: The proband, a male neonate, manifested renal dysplasia, congenital heart disease, pulmonary dysplasia, mediastinal hernia, cryptorchidism, and clavicle dysplasia. WES revealed that he had harbored a heterozygous c.863G>A (p.Arg288Gln) missense variant in exon 6 of PBX1 gene, which resulted substitution of Arginine at position 288 by Glutamine, for which both parents were of the wild type. The variant was unreported previously and rated as pathogenic (PS2+PM1+PM2_Supporting+PP2+PP3) based on the ACMG guidelines. CONCLUSION The c.863G>A variant of the PBX1 gene probably underlay the pathogenesis in the proband. Above finding has enriched the mutational spectrum of the PBX1 gene.
Humans ; Male ; Pre-B-Cell Leukemia Transcription Factor 1/genetics* ; Phenotype ; Infant, Newborn ; Exome Sequencing ; Mutation, Missense ; Heart Defects, Congenital/genetics* ; Abnormalities, Multiple/genetics*

Objective To assess the efficacy of tandem mass spectrometry-specific indicators in diagnosing β-ketothiolase deficiency(BKD)and to elucidate the associated gene variations contributing to the corresponding pathogenic phenotype,thereby facilitating rapid and accurate diagnosis of BKD.Methods Data from tandem mass spectrometry(MS/MS)screening of dried blood spots collected from 16,071 children between January 2018 and December 2021,along with results from gas chromatography-mass spectrometry(GC-MS)analysis and high-throughput sequencing of positive cases,were analyzed retrospectively.The study aimed to evaluate the contribution of specific MS/MS indicators in the clinical diagnosis of BKD and to trace the genetic etiology of this disease.Results Among the 16 071 subjects screened by MS/MS,37 cases(2.30‰)exhibited elevated C5OH levels,41 cases(2.55‰)showed increased C5∶1 levels,and 2 cases were diagnosed with BKD based on GC-MS analysis.When diagnosing BKD using C5OH as a single indicator,the false positive rate was 0.22%,which is lower than that of C5∶1(0.24%).The positive predictive value for C5OH was 5.40%,higher than that of C5∶1(4.88%).Among the 16 071 pediatric patients,only 2 cases were diagnosed with BKD due to elevated C5OH combined with increased C5∶1 levels,resulting in a positive predictive value of 100%.Whole exome sequencing of these two BKD patients revealed that both carried acetyl-CoA acetyltransferase 1(ACAT1)gene double allele missense heterozygous mutations.The four previously unreported mutation sites were c.949G>C(p.Asp317His),c.1063G>A(p.Ala355Thr),c.146G>A(p.Arg49Lys),and c.700G>A(p.Glu234Lys).These findings provide novel insights into the genetic basis of BKD.Conclusions The MS/MS screening indicator C5OH demonstrates superior diagnostic efficacy compared to C5∶1 in diagnosing BKD,as evidenced by lower false positive rates and higher positive predictive values.When diagnosing BKD,the use of combined indicators significantly enhances the accuracy of biochemical diagnosis compared to single indicators.Exome sequencing revealed that all BKD patients carried previously unreported mutations in the ACAT1.

Objective:To analyze the safety and short-term efficacy of thoracic radiotherapy combined with anlotinib in the treatment of inoperable non-small cell lung cancer (NSCLC).Methods:A prospective study was conducted on patients with unresectable locally advanced NSCLC who were intolerant to concurrent chemoradiotherapy and treated at the Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, from October 2020 to September 2023. Anlotinib was administered orally concurrently with radiotherapy (days 1-14, 21 days per cycle, for 3 cycles). Adverse effects and short-term tumor recurrence were observed from the beginning of radiotherapy to the 3-month post-radiotherapy. Kaplan-Meier method was used to calculate progression-free survival (PFS) and overall survival (OS) rates from the date of initial treatment (induction therapy), and intergroup comparisons were performed using the log-rank test.Results:The median age was 62 years (range:42-76 years), with a male predominance ( n=36, 88%) of the included 41 patients. The incidence of grade 3-4 acute hematologic adverse events was 20% (8 cases); the incidence of grade 3 hemoptysis was 2% (1 case), with no grade 4 hemoptysis; the incidence of grade 3-4 radiation pneumonitis was 10% (4 cases). No grade 5 adverse events were observed in the entire cohort. With a median follow-up of 19.7 months (range: 7.1-50.1 months), 19 patients (46%) experienced recurrence, including 4 patients (10%) with local recurrence, 6 patients (15%) with regional lymph node recurrence, and 11 patients (27%) with distant metastases. The 1-year PFS rate was 78.3%. 8 patients (20%) died, including 3 patients died from COVID-19 infection during the follow-up period, 1 patient who died from hypostatic pneumonia due to prolonged bed rest after cerebral infarction, and 4 patients died from tumor-related causes. The 1-year OS rate was 78.0%. Conclusions:Thoracic radiotherapy combined with anlotinib demonstrates good safety, manageable adverse events, and favorable short-term efficacy in NSCNC patients intolerant to concurrent chemoradiotherapy.

Objective:To analyze the prognostic value of systemic inflammatory score (SIS) in patients with unresectable stage Ⅲ non-small cell lung cancer (NSCLC) treated by definitive chemoradiotherapy (dCRT) combined with or without consolidation immunotherapy with immune checkpoint inhibitor (ICI).Methods:The medical record data of 229 patients who received dCRT from January 2014 to December 2017 and 183 patients who received dCRT combined with any form of ICI (induction, concurrent, consolidation or combination) from August 2018 to August 2022 in the Cancer Hospital, Chinese Academy of Medical Sciences were retrospectively analyzed. Upon admission, 1 and 3 months after treatment (efficacy evaluation) and upon tumor recurrence, peripheral blood count was collected, and neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and SIS were calculated, respectively. The SIS before, 1 and 3 months after treatment was defined as SIS 0, SIS 1 and SIS 3, respectively. Overall survival (OS) was considered as the primary endpoint. All patients were divided into dCRT group and dCRT+ICI group according to whether received immunotherapy, and then divided into different subgroups based on the cutoff value of SIS determined by X-Tile software. The prognostic value of SIS was evaluated by Kaplan-Meier survival analysis. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the predictive efficiency. The predictive value of SIS was compared with inflammatory indexes (NLR, PLR) and independent prognostic factors. Results:In the dCRT group, the optimal cutoff value of SIS 0 was 590×10 9 and 530×10 9 in the dCRT+ICIs group. Univariate and multivariate analyses indicated that SIS 0 was an independent predictive factor of OS, progression - free survival (PFS), local - recurrence free survival (LRFS) and distant metastasis free survival (DMFS) in the dCRT group, but not associated with DMFS in the dCRT+ICI group. In the dCRT group, SIS 1>970×10 9 (optimal cutoff value) predicted poor OS ( HR=2.512, 95% CI=1.622-3.198, P<0.001), PFS ( HR=1.726, 95% CI=1.187-2.509, P=0.004), and DMFS ( HR=1.625, 95% CI=1.029-2.564, P=0.037). In the dCRT+ICI group, SIS 3>1570×10 9 (optimal cutoff value) indicated poor OS ( HR=5.107, 95% CI=1.731-15.069, P=0.003). In both groups, the AUC of SIS was higher than NLR, PLR and other traditional clinicopathological predictive indexes except T stage. Conclusions:SIS before treatment can be considered as an independent, dependable and easily acquired prognostic marker in patients with unresectable stage Ⅲ NSCLC treated by dCRT or dCRT+ICI. In the dCRT+ICI group, the optimal time point of post-radiotherapy SIS (3 months after treatment) is postponed than that (1 month after treatment) in the dCRT group.

Objective To analyzing the correlation between serum microRNA(miRNA,miR)-128-3p,miRNA(miR)-126 expression and Gensini score in patients with coronary artery disease.Methods A retrospective study was conducted on 60 patients with coronary artery disease who were treated in the Department of Cardiology,Harrison International Peace Hospital from June 2020 to 2022.They were selected as the observation group,and another 60 patients with non-coronary artery disease who were treated in the hospital during the same period were selected as the control group.Serum miR-128-3p,miR-126 and Gensini scores were measured and compared between the two groups,and compared the serum miR-128-3p,miR-126 and Gensini scores of patients with single,double,and multiple vessel lesions in the observation group.According to the stenosis rate of coronary arteries,they were divided into I degree,II degree,III degree and IV degree groups.The serum miR-128-3p,miR-126 and Gensini scores were compared among different stenosis grading groups.According to the Gensini score,patients were divided into mild and severe lesion groups.According to the Gensini score,patients were divided into mild and severe lesion groups.The serum miR-128-3p and miR-126 levels were compared between the mild and severe lesion groups.Pearson analysis determined the correlation between serum miR-128-3p and miR-126 levels and Gensini score.Receiver operating characteristic curve(ROC)was plotted,and the area under curve(AUC)was calculated to analyze the predictive efficacy of the combined detection of serum miR-128-3p and miR-126 levels for coronary artery disease.Logistic regression analysis of influencing factors of coronary artery disease.Results Compared with the control group,the observation group showed an increase in serum miR-128-3p(4.28±0.52 vs 2.61±0.36)and Gensini score(31.29±5.62 score vs 6.16±1.04 score),observation group showed a decrease in serum miR-126,with statistically significant differences(t=21.678,34.058,11.002,all P<0.05).Compared with the double vessel disease and single vessel disease groups,the serum miR-128-3p and Gensini score in the multi vessel disease group increased(t=4.945,7.171;6.795,11.686),the serum miR-126 decreased(t=3.104,5.033),and the differences were statistically significant(all P<0.05).Compared with the I～II group,the serum miR-128-3p and Gensini score in the III～IV group increased significantly(t=5.590,12.961),the serum miR-126 decreased significantly(t=6.021),with statistical significance differences(all P<0.05).Compared with the mild lesion group,the serum miR-128-3p level increased in the severe lesion group(t=4.056),the serum miR-126 level decreased(t=4.806),and the differences were statistically significant differences(all P<0.05).There was a positive correlation between serum miR-128-3p and Gensini score(r=0.404,P<0.05),and a negative correlation between serum miR-126 and Gensini score(r=-0.393,P<0.05).The AUC of combined detection of serum miR-128-3p and miR-126 was higher than that of single detection,and the differences were statistically significant(Z=2.768,2.152,all P<0.05).The differences in smoking,triglycerides(TG),uric acid(UA),fibrinogen(FIB)between the observation group and the control group were statistically significant(t/χ2=4.231～28.732,all P<0.05).Conclusion Patients with coronary artery disease have high expression of serum miR-128-3p and low expression of serum miR-126,which is correlated with Gensini score.The combined detection of serum miR-128-3p and miR-126 can improve the predictive efficiency of coronary artery disease,and the occurrence of coronary artery disease is related to multiple factors,which should be given clinical attention.

This paper summarized and analyzed various characteristics of meridians and acupoints and their detection technologies in the past 5 years,which screened on PubMed,CNKI(China National Knowledge Infrastructure)database,and Wanfang database.Current studies are primarily focus on the electrical,thermal,and optical characteristics of meridians and acupoints.Utilizing modern technology,devices designed to detect these characteristics have been applied in selecting acupoints,assisting diagnosis,reflecting the effectiveness of acupuncture,and conducting health assessments.The use of external detection devices to explore the physical properties of meridians and acupoints provides more precise technical feedback for substantial research into these areas.However,future efforts must strengthen the comprehensive exploration of meridian and acupoint characteristics and foster interdisciplinary technological integration.This approach will enable a positive development cycle of"detection-feedback-relearning"in the research of meridian and acupoint characteristics.

Objective To explore the predictive value of heel blood thyrotropin stimulating hormone(TSH)and insulin-like growth factor-1(IGF-1)for congenital hypothyroidism(CH).Methods A total of 83 children with CH admitted to the Seventh Medical Center of the Chinese People's Liberation Army General Hospital from January 2021 to January 2024 were selected as the study group,and 53 healthy newborns born and examined in the center during the same period were selected as the control group.Heel blood TSH,IGF-1 and thyroid function were measured in both groups.Heel blood TSH,IGF-1 and thyroid function indexes were compared between the two groups,and the correlation between heel blood TSH,IGF-1 and thyroid function indexes was analyzed,the influencing factors of CH occurrence were analyzed,and the predictive value of heel blood TSH,IGF-1 and thyroid indexes for CH was analyzed.Results Pearson correlation analysis showed that heel blood TSH was negatively correlated with FT4,TT3,FT3 and TT4(r=-0.522,-0.468,-0.539,-0.667,all P＜0.05).IGF-1 was positively correlated with FT4,TT3,FT3,TT4(r=0.394,0.427,0.511,0.562,all P＜0.05).The results of receiver operating characteristic curve analysis showed that the area under the curve of TSH,IGF-1 and their combination were 0.800,0.794 and 0.822,respectively.Univariate and multiple Logistic regression analysis showed that birth weight,family history,TSH,IGF-1,FT4,FT3 were the influencing factors for the occurrence of CH(P＜0.05).Conclusion The combined detection of TSH and IGF-1 levels in heel blood has a certain predictive value for the occurrence of CH,and can provide a basis for the disease assessment of children.