GBA1 gene mutation is an important genetic risk factor for Parkinson’s disease (PD). This paper reports a case of a 43-year-old male PD patient carrying a rare heterozygous Thr408Met mutation in the GBA1 gene identified through whole-exome sequencing, leading to a diagnosis of GBA1-associated PD. The patient’s motor symptoms were primarily characterized by bradykinesia and rigidity, without significant cognitive decline. Treatment with low-dose levodopa combined with a dopamine agonist resulted in significant symptomatic improvement.

Diabetic foot (DF) is one of the most serious chronic complications of diabetes. The incidence rate among global diabetes patients is as high as 15% to 25%, and about 50% of patients will develop contralateral foot ulcers within 5 years after the first unilateral ulcer. As a non-invasive prevention and control solution, the application progress of functional insoles is mainly reflected in the following aspects:(1) Material innovation. The application of new composite materials and smart materials has significantly enhanced the pressure reduction effect and comfort. (2) Structural optimization. The development of multi-layer design and local pressure reduction structure has achieved more precise pressure distribution regulation. (3) Manufacturing process. 3D printing and parametric design have enabled the personalized customization of functional insoles. (4) Intelligent monitoring. It integrates functions such as pressure sensing and temperature monitoring, achieving real-time monitoring and early warning of foot conditions. Clinical research has confirmed that personalized functional insoles could reduce the incidence of foot ulcers and shorten the healing time of ulcers. At present, the research hotspots mainly focus on the development of smart materials, the construction of multi-functional integration and remote monitoring systems. However, in-depth research is still needed in the aspects of biomechanical mechanisms, standardized evaluation systems and long-term efficacy assessment. The development of future functional insoles should focus on the coordinated advancement of "personalization-intelligence-standardization", with the aim of providing more effective solutions for the prevention and treatment of DF.
Humans ; Diabetic Foot/therapy* ; Foot Orthoses

OBJECTIVES: To investigate the clinical features and prognosis of children with non-Down-syndrome-related acute megakaryoblastic leukemia (non-DS-AMKL). METHODS: A retrospective analysis was conducted on the medical data of 17 children with non-DS-AMKL who were admitted to Children's Hospital of The First Affiliated Hospital of Zhengzhou University from January 2013 to December 2023, and their clinical features, treatment, and prognosis were summarized. RESULTS: Among the 17 children with non-DS-AMKL, there were 8 boys and 9 girls. Fourteen patients had an onset age of less than 36 months, with a median age of 21 months (range:13-145 months). Immunophenotyping results showed that 16 children were positive for CD61 and 13 were positive for CD41. The karyotype analysis was performed on 16 children, with normal karyotype in 6 children and abnormal karyotype in 9 children, among whom 5 had complex karyotype and 1 had no mitotic figure. Detected fusion genes included EVI1, NUP98-KDM5A, KDM5A-MIS18BP1, C22orf34-BRD1, WT1, and MLL-AF9. Genetic alterations included TET2, D7S486 deletion (suggesting 7q-), CSF1R deletion, and PIM1. All 17 children received chemotherapy, among whom 16 (94%) achieved complete remission after one course of induction therapy, and 1 child underwent hematopoietic stem cell transplantation (HSCT) and remained alive and disease-free. Of all children, 7 experienced recurrence, among whom 1 child received HSCT and died of graft-versus-host disease. At the last follow-up, six patients remained alive and disease-free. CONCLUSIONS Non-DS-AMKL primarily occurs in children between 1 and 3 years of age. The patients with this disorder have a high incidence rate of chromosomal abnormalities, with complex karyotypes in most patients. Some patients harbor fusion genes or gene mutations. Although the initial remission rate is high, the long-term survival rate remains low.
Humans ; Male ; Female ; Leukemia, Megakaryoblastic, Acute/etiology* ; Child, Preschool ; Infant ; Child ; Retrospective Studies ; Prognosis ; Down Syndrome/complications*

OBJECTIVE: To explore the neuroprotective effects of Xuefu Zhuyu Decoction (XFZYD) based on in vivo and metabolomics experiments. METHODS: Traumatic brain injury (TBI) was induced via a controlled cortical impact (CCI) method. Thirty rats were randomly divided into 3 groups (10 for each): sham, CCI and XFZYD groups (9 g/kg). The administration was performed by intragastric administration for 3 days. Neurological functions tests, histology staining, coagulation and haemorheology assays, and Western blot were examined. Untargeted metabolomics was employed to identify metabolites. The key metabolite was validated by enzyme-linked immunosorbent assay and immunofluorescence. RESULTS: XFZYD significantly alleviated neurological dysfunction in CCI model rats (P<0.01) but had no impact on coagulation function. As evidenced by Evans blue and IgG staining, XFZYD effectively prevented blood-brain barrier (BBB) disruption (P<0.05, P<0.01). Moreover, XFZYD not only increased the expression of collagen IV, occludin and zona occludens 1 but also decreased matrix metalloproteinase-9 (MMP-9) and cyclooxygenase-2 (COX-2), which protected BBB integrity (all P<0.05). Nine potential metabolites were identified, and all of them were reversed by XFZYD. Adenosine was the most significantly altered metabolite related to BBB repair. XFZYD significantly reduced the level of equilibrative nucleoside transporter 2 (ENT2) and increased adenosine (P<0.01), which may improve BBB integrity. CONCLUSIONS XFZYD ameliorates BBB disruption after TBI by decreasing the levels of MMP-9 and COX-2. Through further exploration via metabolomics, we found that XFZYD may exert a protective effect on BBB by regulating adenosine metabolism via ENT2.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Blood-Brain Barrier/metabolism* ; Brain Injuries, Traumatic/metabolism* ; Adenosine/metabolism* ; Male ; Rats, Sprague-Dawley ; Rats

Objective To explore the effect and mechanism of salvianolic acid B on bronchial epithelial cell apoptosis induced by cigarette smoke extract.Methods Human bronchial epithelial cells 16HBE were divided into control group,model group(induced by cigarette smoke extract),experimental low-dose group(induced by cigarette smoke extract+11 μmol·L-1 salvianolic acid B treatment),and experimental medium-dose group(cigarette smoke extract Induction+22 μmol·L-1 salvianolic acid B treatment),experimental high-dose group(cigarette smoke extract induction+44 μmol·L-1 salvianolic acid B treatment),experimental high-dose+Compound C group(cigarette smoke extract induction+44 μmol·L-1 Salvianolic acid B+AMPK signaling pathway inhibitor Compound C treatment).Cell counting kit-8(CCK-8)assay was used to detect proliferation;Western blot was used to detect the phosphorylated adenosine monophosphate activates protein kinase(p-AMPK),CCAAT/enhancer-binding protein C/EBP(CHOP),activating transcription factor 4(ATF4)protein expression;PI single staining was used to detect cell cycle;Annexin V-FITC/PI double staining was used to detect apoptosis,and spectrophotometry was used to detect caspase-3 activity.Results The cell proliferation activity(OD value)in the bronchial epithelial cells of the control group,model group,experimental low-dose group,experimental medium-dose group,experimental high-dose group,and experimental high-dose+Compound C group were 0.86±0.07,0.38±0.03,0.45±0.03,0.54±0.04,0.68±0.03 and 0.42±0.04;the expression levels of p-AMPK/AMPK protein were 0.41±0.03,0.13±0.03,0.20±0.02,0.28±0.04,0.36±0.04 and 0.22±0.02;G0/G1 phase were(54.40±5.84)％,(82.93±4.50)％,(75.45±4.73)％,(67.41±2.70)％,(59.15±3.73)％and(69.80±6.59)％;apoptosis rate were(3.21±0.49)％,(24.90±3.35)％,(20.56±1.73)％,(13.55±1.68)％,(9.20±1.07)％and(18.04±1.79)％.Compared experimental low-dose group,experimental medium-dose group,experimental high-dose group with model group,the difference of above indicators were all statistically significant(all P＜0.05);compared the experimental high-dose+Compound C group with the experimental high-dose group,the difference of above indicators were all statistically significant(all P＜0.05).Conclusion Salvianolic acid B affects endoplasmic reticulum stress by activating AMPK signaling to reduce bronchial epithelial cell apoptosis induced by cigarette smoke extract.

Objective To cultivate glioblastoma U87 stem-like cells(SLCs)and to detect the level of stemness bio-markers,mitochondrial respiratory capacity and the capacity of in vivo tumorigenesis.Methods B-27,growth factors EGF and bFGF was added into DMEM/F-12 culture in serum-free stem cell culture medium for U87 SLCs.Suspended culture of U87 SLCs was suspended using the neuro-sphere formation assay,while adherent culture of U87 SLCs was achieved by coating Matrigel matrix on the culture surface.The mRNA and protein level of stemness biomarkers in culture were detected using real-time quantitative PCR and Western blot.The proportion of CD133+cells in culture was detected by flow cytometry.The changes of cell oxygen consumption rate were detected by Seahorse cell metabo-lism analysis.Cell tumorigenesis ability was verified by subcutaneous tumor transplantation in animals.Results U87 SLCs in stem cell culture medium would grow into typical sphere morphology within one week,and the spheres would continue to grow as the culture process prolongs.At the appropriate concentration of adhesive,U87 SLCs adhered to and grow well in stem cell culture medium.The mRNA transcription of stemness biomarkers such as CD133,nes-tin,OLIG2,CD44,CD15,and integrin α6(ITGA6)was significantly increased as found in both culture methods,and the protein levels of CD133 and nestin were also increased under both methods(P＜0.05).U87 SLCs showed higher mitochondrial reserve respiratory capacity(P＜0.05).U87 SLCs could form larger subcutaneous tumors with fewer inoculated cells(P＜0.05),and grew faster in vivo with stronger tumorigenic ability.Conclusions U87 SLCs have typical stemness characteristics and may function as tumor cell model with higher stemness properties.

Objective To study the effect of carboxyamidotriazole-orotate(CTO)on the proliferation and fatty acid anabolism regulation of human pancreatic cancer cells.Methods Human pancreatic cancer cell lines AsPC-1,AsPC-1/GEM(AR),PANC-1 and MiaPaCa-2 were used as the study subjects;cell survival rate was detected by sulfo-nylrhodamine B(SRB);the mRNA level of key genes for fatty acid synthesis was detected by qPCR;the protein level of the AMPK/ACC pathway was detected by Western blot;intracellular lipid metabolites were examined by liquid chromatography-mass spectrometry(LC-MS).Results Comparing to control group,CTO significantly de-creased the cell viability of AsPC-1,AR,PANC-1,and MiaPaCa-2(P＜0.05).CTO down-regulated the mRNA level of key fatty acid synthesis genes(P＜0.05).CTO significantly reduced the protein expression of AMPK,ACC and c-Myc(P＜0.05),while increasing the protein expression of p-AMPK and p-ACC(P＜0.05).CTO decreased lipid metabolite content in AR cells(P＜0.05).Conclusions CTO attenuates cellular fatty acid anabolism by inhibition of oncogene c-Myc expression and AMPK/ACC pathway,down-regulates the expression of fatty acid synthesis-related genes,and then inhibits proliferation of the human pancreatic cancer cell lines AsPC-1,AR,PANC-1 and MiaPaCa-2.

AIM:To investigate the role and molecular mechanisms of SMARCA4(SWI/SNF-related,matrix-associated,actin-dependent regulator of chromatin,subfamily A,member 4)in ferroptosis.METHODS:(1)Human fi-brosarcoma HT1080 cells were treated with dimethyl sulfoxide(DMSO)and different concentrations(31.25,62.5 and 125 nmol/L)of Ras-selective lethal small molecule 3(RSL3;ferroptosis inducer).Each treatment had 3 replicate wells of cells.The protein levels of SMARCA4 were detected by Western blot.(2)Two small interfering RNAs(siSMARCA4-1 and siSMARCA4-2)were constructed according to the SMARCA4 gene sequence.After SMARCA4 knockdown,each treat-ment had 3 replicate wells of cells,and the protein levels of SMARCA4 were determined by Western blot.Effects of DMSO,necrostatin 2 racemate(Nec-1s;necroptosis inhibitor),Z-VAD(OMe)-FMK(Z-VAD,pan-caspase inhibitor/apoptosis inhibitor)and ferrostatin-1(Fer-1,ferroptosis inhibitor)on cell viability were assessed using high-content analy-sis.The levels of ferroptosis indicators,including prostaglandin-endoperoxide synthase 2(PTGS2)transcription,lipid peroxidation,reactive oxygen species(ROS),labile iron pool(LIP)and glutathione,were determined by RT-qPCR and flow cytometry.The mRNA expression levels of pivotal iron metabolism genes,ferroptosis-related ROS regulatory genes,and cholesterol synthesis-related genes were measured using RT-qPCR.Impact of cholesterol on the cell viability were as-sessed using high-content analysis.(3)Common differential gene analysis and gene ontology(GO)enrichment analysis were performed on published online data.RESULTS:(1)Treatment with RSL3 significantly reduced the protein level of SMARCA4(P＜0.05).(2)Knockdown of SMARCA4 resulted in ferroptosis.(3)Knockdown of SMARCA4 did not induce ferroptosis by modulating the LIP and the transcription levels of ROS-related genes.(4)Knockdown of SMARCA4 affected the pathways associated with the cell membrane,lipid raft,and cholesterol synthesis.(5)Addition of cholesterol to cell culture medium rescued the ferroptosis induced by SMARCA4 knockdown(P＜0.01).CONCLUSION:Treatment with RSL3 reduces the protein level of SMARCA4 in human fibrosarcoma HT1080 cells,and inhibition of cholesterol synthesis by SMARCA4 knockdown leads to the ferroptosis of HT1080 cells.

Objective To analyze the influencing factors for catheter-associated infection(CAI)in chemotherapy treated patients after indwelling peripherally inserted central catheter(PICC)based on a random forest model.Methods 400 tumor patients who received chemotherapy and PICC were selected and divided into the training set(n=300)and the test set(n=100)in a 3∶1 ratio through computer-generated random number.Patients in the training set were subdivided into the non-infection group and the infection group based on the occurrence of infec-tion.Clinical data from two groups of patients were compared.Influencing factors for the occurrence of CAI after PICC were analyzed with multivariate logistic regression model and the integrated classification algorithm of random forest model,and the predictive performance of the two methods was compared.Results Among 300 chemotherapy treated patients in the training set,32 cases(10.67％)experienced CAI.Compared with the non-infection group,patients in the infection group had more single punctures for catheterization,longer PICC retention time,larger pro-portion of catheter movement,larger proportion of complication with diabetes,higher frequency of dressing chan-ges,lower white blood cell count and immune function(all P＜0.05).PICC retention time,catheter movement,complication with diabetes,dressing change frequency,white blood cell(WBC)and immune function were inde-pendent influencing factors for CAI after PICC(all P＜0.05).The random forest model showed that ranking by the importance of different influencing factors was as following:PICC retention time,catheter movement,complication with diabetes,WBC,dressing change frequency and immune function.The integrated classification algorithm of random forest model for predicting the occurrence of CAI in chemotherapy treated patients showed that the area un-der the receiver operating characteristic(ROC)curve(AUC)was 0.872,which had better prediction performance compared with the logistic regression model(AUC=0.791).Conclusion PICC retention time,catheter movement,complicated with diabetes,dressing change frequency,WBC level and immune function are independent influencing factors for CAI in chemotherapy treated patients.The integrated classification algorithm of random forest model can be used to predict CAI in chemotherapy treated patients,and its prediction performance is better than that of the logistic regression model.

Objective To understand the pathogen detection of hospitalized patients before antimicrobial therapy in a hospital through implementation of comprehensive intervention measures,and provide reference basis for the de-velopment of targeted measures.Methods Hospitalized patients who received therapeutic antimicrobial agents in this hospital were selected as the research subjects.Patients who were hospitalized from January to May 2022 were selected as the pre-intervention group,comprehensive intervention measures were taken from June to October 2022,and those who were hospitalized from November 2022 to March 2023 were selected as the post-intervention group.The pathogen detection rate before antimicrobial therapy,sterile specimen detection rate,antimicrobial use rate,de-tection rate of key multidrug-resistant organisms of patients before and after the intervention were analyzed.Results Compared to before intervention,the proportion of pathogen detection rate before antimicrobial therapy(62.09％vs 74.04％),detection rate of healthcare-associated infection diagnosis-related pathogens(62.82％vs 92.73％),and sterile specimen detection rate(35.17％vs 41.06％)of hospitalized patients after intervention all increased signifi-cantly,with statistically significant differences(all P＜0.05).After intervention,pathogen detection rate before the combination use of key antimicrobial agents was not statistically different from before intervention(93.33％vs 90.48％,P＞0.05),while antimicrobial use rate was lower than before intervention(39.93％vs 44.95％,P＜0.05).There was no statistically significant difference in the detection rate of key multidrug-resistant organisms be-fore and after intervention(all P＞0.05).Conclusion Adopting scientific and rational intervention measures can improve the pathogen detection rate,provide a reference basis for the rational use of antimicrobial agents.There was no significant improvement in the pathogen detection rate before the combination use of key antimicrobial agents and the detection rate of key multidrug-resistant organisms,indicating that relevant measures still need to be further optimized.