Objective : To explore the expression profile of core 1 β1,3-galactosyltransferase 1(C1GALT1) in glioblastoma(GBM) and to elucidate its impact on the initiation and progression of GBM. Methods : The expression levels and prognostic significance of C1GALT1 in GBM were analyzed using the GEPIA and CGGA databases. Two representative glioblastoma cells(U251 and LN18) were selected to construct C1GALT1-knockdown cell lines and performed in vitro experiments. The Cell Counting Kit-8(CCK-8) and Transwell assays were employed to evaluate the impact of C1GALT1 on proliferation, migration and invasion of GBM cells. Transcriptome data were analyzed to identify potential signaling pathways. Senescence β-Galactosidase Staining Kit was used to detect β-galactosidase activity. Results : nalysis of GEPIA and CGGA databases revealed that C1GALT1 was significantly upregulated in GBM tissues compared to adjacent non-cancerous tissues (P < 0. 05) , and its high expression was associated with poor prognosis of patients (P < 0. 000 1) . The CCK-8 experiment demonstrated a significant reduction in prolifera- tion rate following C1GALT1 knockdown (P < 0. 05) . Transwell assay showed that cell migration and invasion de- creased after C1GALT1 was knocked down ( P < 0. 001) . Transcriptome sequencing and senescence β-galactosi- dase staining showed that C1GALT1 was involved in the cellular senescence signaling pathway , and the activity of β-galactosidase associated with cellular senescence significantly increased after C1GALT1 was knocked down(P < 0. 05) . Conclusion C1GALT1 is overexpressed in GBM tissues and may promote the proliferation , migration and invasion of GBM cells by inhibiting cellular senescence .

Cervical spine health issues not only seriously affect patients' quality of life but also impose a heavy burden on the social healthcare system. Existing guidelines lack sufficient clinical guidance on lifestyle and work habits, such as exercise, posture, daily routine, and diet, making it difficult to meet practical needs. To address this, relying on the China Association of Chinese Medicine, Wangjing Hospital of China Academy of Chinese Medical Sciences took the lead and joined hands with more than ten institutions to form a multidisciplinary guideline development group. For the first time, the group developed the Guidelines for Cervical Spine Health Intervention based on evidence-based medicine methods, strictly following the standardized procedures outlined in the World Health Organization Handbook for Guideline Development and the Guiding Principles for the Formulation/Revision of Clinical Practice Guidelines in China (2022 Edition). This proposal systematically explains the methods and steps for developing the guideline, aiming to make the guideline development process scientific, standardized, and transparent.
Humans ; Practice Guidelines as Topic/standards* ; Cervical Vertebrae ; China

The glymphatic system(GS)is a unique toxic sub-stance clearance system in brain,which is very important for maintaining the microenvironment stability of the central nervous system.The polarization distribution of aquaporin 4(AQP4)lo-cated in the terminal foot of astrocytes affects the function of GS and participates in the pathological progress of many neurodegen-erative diseases,but the detailed regulation mechanism of AQP4 polarization distribution has not been systematically summarized.Therefore,this paper systematically combs the mechanism of reg-ulating the polarization distribution of AQP4 from the perspective of the composition integrity of dystrophin-glycoprotein complex(DGC)and basement membrane foot complex,and summarizes the potential drug and non-drug therapies for targeted regulation of AQP4 polarization distribution at present,aiming at providing new target reference and theoretical basis for targeted regulation of AQP4 polarization to prevent and treat neurodegenerative dis-eases.

The glymphatic system(GS)is a unique toxic sub-stance clearance system in brain,which is very important for maintaining the microenvironment stability of the central nervous system.The polarization distribution of aquaporin 4(AQP4)lo-cated in the terminal foot of astrocytes affects the function of GS and participates in the pathological progress of many neurodegen-erative diseases,but the detailed regulation mechanism of AQP4 polarization distribution has not been systematically summarized.Therefore,this paper systematically combs the mechanism of reg-ulating the polarization distribution of AQP4 from the perspective of the composition integrity of dystrophin-glycoprotein complex(DGC)and basement membrane foot complex,and summarizes the potential drug and non-drug therapies for targeted regulation of AQP4 polarization distribution at present,aiming at providing new target reference and theoretical basis for targeted regulation of AQP4 polarization to prevent and treat neurodegenerative dis-eases.

Atrial fibrillation(AF)is the most prevalent sustained cardiac arrhythmia among humans,with its incidence increasing significantly with age.Despite the high frequency of AF in clinical practice,its etiology and management remain elusive.To develop effective treatment strategies,it is imperative to comprehend the underlying mechanisms of AF;therefore,the establishment of animal models of AF is vital to explore its pathogenesis.While spontaneous AF is rare in most animal species,several large animal models,particularly those of pigs,dogs,and horses,have proven as invaluable in recent years in advancing our knowledge of AF pathogenesis and developing novel therapeutic options.This review aims to provide a comprehensive discussion of various animal models of AF,with an emphasis on the unique features of each model and its utility in AF research and treatment.The data summarized in this review provide valuable insights into the mechanisms of AF and can be used to evaluate the efficacy and safety of novel therapeutic interventions.

Objective:To evaluate the efficacy of acute T-cell lymphoblastic leukemia(T-ALL)in children and explore the prognostic risk factors.Methods:The clinical data of 127 newly diagnosed children with T-ALL admitted to five hospitals in Fujian province from April 2011 to December 2020 were retrospectively analyzed,and compared with children with newly diagnosed acute precursor B-cell lymphoblastic leukemia(B-ALL)in the same period.Kaplan-Meier analysis was used to evaluate the overall survival(OS)and event-free survival(EFS),and COX proportional hazard regression model was used to evaluate the prognostic factors.Among 116 children with T-ALL who received standard treatment,78 cases received the Chinese Childhood Leukemia Collaborative Group(CCLG)-ALL 2008 protocol(CCLG-ALL 2008 group),and 38 cases received the China Childhood Cancer Collaborative Group(CCCG)-ALL 2015 protocol(CCCG-ALL 2015 group).The efficacy and serious adverse event(SAE)incidence of the two groups were compared.Results:Proportion of male,age ≥ 10 years old,white blood cell count(WBC)≥ 50 × 109/L,central nervous system leukemia,minimal residual disease(MRD)≥ 1％during induction therapy,and MRD ≥ 0.01％at the end of induction in T-ALL children were significantly higher than those in B-ALL children(P＜0.05).The expected 10-year EFS and OS of T-ALL were 59.7％and 66.0％,respectively,which were significantly lower than those of B-ALL(P＜0.001).COX analysis showed that WBC ≥ 100 x 109/L at initial diagnosis and failure to achieve complete remission(CR)after induction were independent risk factors for poor prognosis.Compared with CCLG-ALL 2008 group,CCCG-ALL 2015 group had lower incidence of infection-related SAE(15.8％vs 34.6％,P=0.042),but higher EFS and OS(73.9％vs 57.2％,PEFS=0.090;86.5％vs 62.3％,PoS=0.023).Conclusions:The prognosis of children with T-ALL is worse than children with B-ALL.WBC ≥ 100 × 109/L at initial diagnosis and non-CR after induction(especially mediastinal mass has not disappeared)are the risk factors for poor prognosis.CCCG-ALL 2015 regimen may reduce infection-related SAE and improve efficacy.

Objective:To analyze the related factors of treatment failure in children with acute lymphoblastic leukemia (ALL)in real-world.Methods:The clinical data of 1414 newly diagnosed children with ALL admitted to five hospital in Fujian province from April 2011 to December 2020 were retrospectively analyzed.Treatment failure was defined as relapse,non-relapse death,and secondary tumor.Results:Following-up for median time 49.7 (0.1-136. 9)months,there were 269 cases (19.0％)treatment failure,including 140 cases (52.0％)relapse,and 129 cases (48.0％)non-relapse death.Cox univariate and multivariate analysis showed that white WBC≥50 ×109/L at newly diagnosis,acute T-cell lymphoblastic leukemia (T-ALL),BCR-ABL1,KMT2A-rearrangement and poor early treatment response were independent risk factor for treatment failure (all HR>1.000,P<0.05).The 5-year OS of 140 relapsed ALL patients was only 23.8％,with a significantly worse prognosis for very early relapse (relapse time within 18 months of diagnosis).Among 129 patients died from non-relapse death,71 cases (26.4％)were died from treatment-related complications,56 cases (20.8％)died from treatment abandonment,and 2 cases (0.7％)died from disease progression.Among them,treatment-related death were significantly correlated with chemotherapy intensity,while treatment abandonment were mainly related to economic factors.Conclusion:The treatment failure of children with ALL in our province is still relatively high,with relapse being the main cause of treatment failure,while treatment related death and treatment abandonment caused by economic factors are the main causes of non-relapse related death.

OBJECTIVES: To study the clinical features and prognosis of high hyperdiploid (HHD) childhood acute lymphoblastic leukemia (ALL). METHODS: A retrospective analysis was performed on the medical data of 1 414 children who were newly diagnosed with ALL and were admitted to five hospitals in Fujian Province of China from April 2011 to December 2020. According to karyotype, they were divided into two groups: HHD (n=172) and non-HHD (n=1 242). The clinical features and treatment outcome were compared between the two groups, and the factors influencing the prognosis were further explored. RESULTS: Among the 1 414 children with ALL, 172 (12.16%) had HHD. Compared with the non-HHD group, the HHD group had significantly lower proportions of children with risk factors for poor prognosis at diagnosis (age of onset ≥10 years or <1 year, white blood cell count ≥50×10⁹/L, and T-cell phenotype) or positive fusion genes (TEL-AML1, BCR-ABL1, E2A-PBX1, and MLL gene rearrangement) (P<0.05). The HHD group had a significantly higher proportion of children with minimal residual disease (MRD) <0.01% at the end of induction chemotherapy (P<0.05). The 10-year event-free survival (EFS) rate and overall survival (OS) rate in the HHD group were significantly higher than those in the non-HHD group (P<0.05). The univariate analysis showed that the number of chromosomes of 58-66, trisomy of chromosome 10, trisomy of chromosome 17, bone marrow MRD <1% on day 15 or 19 of induction chemotherapy, and bone marrow MRD <0.01% on day 33 or 46 of induction chemotherapy were associated with a higher EFS rate (P<0.05), and trisomy of chromosome 10 was associated with a higher OS rate (P<0.05). The multivariate Cox analysis showed that trisomy of chromosome 17 was closely associated with a high EFS rate (P<0.05). CONCLUSIONS The ALL children with HHD have few risk factors for poor prognosis at diagnosis and often have good prognosis. The number of chromosomes and trisomy of specific chromosomes are associated with prognosis in these children.
Child ; Humans ; Retrospective Studies ; Trisomy ; Prognosis ; Treatment Outcome ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis* ; Neoplasm, Residual ; Disease-Free Survival

Abstract OBJECTIVE To investigate the effect of isodon ternifolia-containing serum(ITS) on the activation of rat primary hepatic Kupffer cell(KC) induced by lipopolysaccharide(LPS) through TLR4/NF-κB/NLRP3 signal pathway. METHODS The primary KC of rats were isolated and cultured, and the primary KC induced by LPS were divided into blank control group, model control group, blank serum group, positive control group(colchicine containing serum group), ITS group, TLR4 blocker group and TLR4 blocker+ITS group. MTT assay was used to detect the effect of different concentrations of ITS on the proliferation activity of KC. The content of interleukin-1β(IL-1β), interleukin-18(IL-18), tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in KC supernatant were detected by ELISA. Fluorescence quantitative polymerase chain reaction(PCR), Western blotting and immunofluorescence were used to detect the expression of TLR4, nuclear factor κB inhibitor protein α(IκBα), cysteine protease-1(Caspase-1), NLRP3 mRNA and TLR4, IκBα, phosphorylated IκBα(p-IκBα), Caspase-1, NLRP3 and NF-κBp65 in KC. RESULTS Compared with the model control group, the contents of IL-1β, IL-18, TNF-α and IL-6 in the supernatant of KC and the expression of TLR4, IκB α, Caspase-1, NLRP3 mRNA and TLR4, IκBα, p-IκBα, Caspase-1, NLRP3, NF-κBp65 protein in the supernatant of KC in all drug groups were down-regulated or decreased(P<0.05 or P<0.01). Compared with TLR4 blocker group, the improvement of most of the above indexes in TLR4 blocker+ITS group was more obvious. CONCLUSION Isodon ternifolia may inhibit the activation of KC and reduce the expression and release of inflammatory factors by down-regulating TLR4/NF-κB/NLRP3 signal pathway, thus alleviating the inflammatory injury of liver.

Objective:To investigate the clinical characteristics and prognostic factors of TCF3-PBX1 fusion gene-positive childhood B-cell precursor acute lymphoblastic leukemia (B-ALL).Methods:The clinical data of 1 287 newly diagnosed children with B-ALL who were admitted to five hospital in Fujian province (Fujian Medical University Union Hospital, the First Affiliated Hospital of Xiamen University, Zhangzhou Affiliated Hospital of Fujian Medical University, Quanzhou First Hospital Affiliated to Fujian Medical University, Nanping First Hospital of Fujian Province) from April 2011 to December 2020 were retrospectively analyzed. According to the results of TCF3-PBX1 fusion gene testing, all the patients were divided into TCF3-PBX1-positive group and TCF3-PBX1-negative group. The clinical characteristics, early treatment response [minimal residual disease (MRD) at middle stage and end of induction chemotherapy] and long-term efficacy [overall survival (OS) and event-free survival (EFS)] of the patients in both groups were compared. Kaplan-Meier method was used for survival analysis. The prognostic factors of TCF3-PBX1-positive B-ALL were analyzed by using Cox proportional hazards model. Among 83 children with TCF3-PBX1-positive B-ALL, the treatment regimens, risk stratification and efficacy evaluation of 62 cases were performed by using Chinese Children's Leukemia Group (CCLG)-ALL 2008 regimen and 21 cases were performed by using Chinese Children's Cancer Group (CCCG)-ALL 2015 regimen, and the efficacy and incidence of serious adverse events (SAE) between the two groups compared.Results:Among 1 287 B-ALL patients, 83 patients (6.4%) were TCF3-PBX1-positive. The proportion of patients with initial white blood cell count (WBC)≥50×10 9/L in the TCF3-PBX1-positive group was higher than that in the TCF3-PBX1-negative group, while the proportions of patients with MRD ≥1% on induction chemotherapy day 15 or day 19, and MRD ≥0.01% on induction chemotherapy day 33 or day 46 in the TCF3-PBX1-positive group were lower than those in the TCF3-PBX1-negative group (all P < 0.05). Univariate Cox regression analysis showed that MRD ≥1% on induction chemotherapy day 15 or day 19 and TCF3-PBX1 ≥0.01% on induction chemotherapy day 33 or day 46 were risk factors for OS and EFS (all P < 0.05). Multivariate analysis showed that MRD ≥1% on induction chemotherapy day 15 or day 19 was an independent risk factor for OS ( HR = 10.589, 95% CI 1.903-58.933, P = 0.007) and EFS ( HR = 10.218, 95% CI 2.429-42.980, P = 0.002). TCF3-PBX1≥0.01% on induction chemotherapy day 33 or day 46 was an independent risk factor for EFS ( HR = 6.058, 95% CI 1.463-25.087, P = 0.013) but not for OS ( HR = 3.550, 95% CI 0.736-17.121, P = 0.115). The 10-year EFS and OS rates of the TCF3-PBX1-positive group were 84.6% (95% CI 76.9%-93.1%) and 89.1% (95% CI 82.1%-96.6%), and the differences between the two groups were not statistically significant (both P > 0.05). Among 80 children who received standardized treatment, compared with children who were treated with CCLG-ALL 2008 regimen, the incidence of infection-related SAE was lower in children who were treated with CCCG-ALL 2015 regimen [0 (0/21) vs. 20.3% (12/59), χ2 = 5.22, P = 0.022], but there were no statistical differences in treatment-related mortality, relapse rate, EFS and OS between the two groups (all P > 0.05). Conclusions:Children with TCF3-PBX1-positive B-ALL have a good prognosis, and MRD≥1% at middle stage of induction chemotherapy and TCF3-PBX1≥0.01% at the end of induction chemotherapy may be influencing factors for poor prognosis. CCCG-ALL 2015 regimen can reduce infection-related SAE while achieving good efficacy.