Methods: This retrospective cohort study included 153 single-level OLIF cases between January 2016 and December 2023. Postoperative computed tomography was used to classify patients into central fusion, lateral fusion, and non-fusion groups. Demographic, surgical, and radiographic parameters—including osteophyte grade, Hounsfield unit (HU) values, and cage positioning—were analyzed to identify factors affecting fusion. Cage subsidence and clinical outcomes (Oswestry Disability Index [ODI], Visual Analog Scale) were compared across groups. Results: Lateral fusion occurred in 39.9% of cases, central in 56.9%, and non-fusion in 3.2%. Preoperative osteophytes and higher HU values were associated with lateral fusion (p<0.001). OLIF with standalone cages (OLIF-SA) had a significantly higher lateral fusion rate than OLIF with posterior screw fixation (OLIF-PS) (p=0.002). Smoking was a significant risk factor for non-fusion (p=0.005). No significant difference in cage subsidence was observed between central and lateral fusion, but non-fusion showed more severe subsidence. Clinical outcomes improved across fusion groups, though non-fusion cases had worse ODI scores at follow-up. Conclusions Lateral fusion is a distinct OLIF feature influenced by osteophytes, bone density, and fixation type. It does not negatively affect cage subsidence or outcomes, but solid fusion remains essential for recovery. These findings enhance understanding of OLIF fusion and may guide surgical planning.

Background/Aims: Cholangiocarcinoma (CCA) is a primary malignant neoplasm with an extremely poor prognosis. While combined chemoradiotherapy has been demonstrated to delay CCA progression to a certain extent, the absence of specific molecular biomarkers or targets significantly hinders the diagnosis and treatment of CCA. Methods: Through cross-analysis of proteomics and ADMA modificationomics, we identified DDX1 overexpressed in CCA with elevated R602-ADMA modifications. HPLC-MS/MS identified PRMT1 as the methyltransferase and USP10 as the deubiquitinating enzyme for DDX1. Immunofluorescence and nuclear-cytoplasmic partitioning experiments confirmed DDX1’s nuclear localization. GO and KEGG analyses clarify the biological functions of DDX1 in response to hypoxia. RNA-seq transcriptomics analyzed key pathways influenced by DDX1. A hydrodynamic in situ CCA mouse model was established to validate the chemopreventive effects of the PRMT1-specific inhibitor GSK715 on CCA development. Results: DDX1 promotes CCA progression both in vivo and in vitro and can be inhibited by GSK715. Mechanistically, PRMT1 mediates ADMA modification at position R602 of DDX1. This modification promotes DDX1 nuclear localization by recruiting USP10 to deubiquitinate DDX1, while simultaneously inhibiting PRMT1 degradation. DDX1 promotes the transcription of PRMT1 and USP10 by binding to the mRNA 3’UTR region, establishing a positive feedback regulatory pathway. This mechanism promotes the occurrence and development of CCA and can serve as a target for the inhibitor GSK715 to suppress CCA progression. Conclusions Our study identified DDX1-R602-ADMA modification as a novel ADMA modification in CCA. It further confirmed its pivotal role in CCA progression. Targeting the USP10-PRMT1-DDX1 axis may represent a significant therapeutic approach for CCA.

China's Medical Service Price(MSP)reform has entered a new phase,implementing management measures.The compilation,implementation,and coordination of MSP item guidelines and the existing contradictions and problems were reviewed.It proposes strengthening price item management in planning under the background of the new era,itemizing in the alignment particle size,and comparing prices in the same coordinate system.This can offer systematic approaches and innovative strategies for improving the quality and efficiency of deepening MSP reform.

BACKGROUND:The blood-brain barrier is an important structure that protects the central nervous system,and the study of the effects of high glucose on the blood-brain barrier is important for the prevention of high glucose-induced damage to the central nervous system.OBJECTIVE:To investigate the potential effect of high glucose on the blood-brain barrier function of hCMEC/D3 human brain microvascular endothelial cells.METHODS:hCMEC/D3 cells were cultured in regular sugar medium(glucose concentration of 25 mmol/L)and high-sugar medium(glucose concentration of 55 mmol/L).The morphology of cells in each group was observed by light microscopy.CCK-8 assay was used to detect changes in cell viability.A monolayer blood-brain barrier model was established using hCMEC/D3 cell line with Transwell chamber device.Changes in cell transmembrane resistance were monitored daily.The permeability of cell monolayers was detected by phenol red permeability.Flow cytometry was used to detect the apoptosis rate of the cells.Western blot assay was used to detect the expression of Bcl-2,Bax,Caspase-3,ZO-1,Occludin,Claudin-1,and histone deacetylase 4.The levels of histone deacetylase in cell supernatant were detected by ELISA.The expression of histone deacetylase 4 in cells was detected by immunofluorescence.RESULTS AND CONCLUSION:(1)The cell viability of high sugar group was significantly lower than that of control group(P＜0.000 1).(2)The cells of the control group were in a good growth state,interwoven into a dense mesh,with interconnections between synapses.The cell growth of high glucose group was suppressed,and the connection of inter-cellular synapses was reduced.(3)Compared with the control group,the transmembrane resistance value of the high glucose group was reduced(P＜0.05);phenol-red permeability of the monolayer cell membrane was increased(P＜0.05);cell apoptosis rate was increased(P＜0.01);the expression of Bax protein was increased(P＜0.000 1);the expression of Caspase-3 protein had no significant change(P＞0.05);the expression of Bcl-2,ZO-1,Occludin,Claudin-1,and histone deacetylase 4 proteins was decreased(P＜0.01,P＜0.001,P＜0.01,P＜0.000 1,P＜0.01);the fluorescence expression of histone deacetylase 4 was decreased(P＜0.001)in the high glucose group.(4)The level of histone deacetylase 4 in the cell supernatant of the high glucose group was lower than that of the control group(P＜0.05).The results show that high glucose induces the increased apoptosis and enhances permeability of hCEMCE/D3 cells,and its mechanism may be related to the decreased expression level of histone deacetylase 4.

The incidence of chronic venous disease(CVD)is significantly higher in the elderly population compared to non-elderly individuals,with more severe disease manifestations.Additionally,elderly CVD patients often have comorbid conditions such as cardiovascular diseases,making the evaluation process more complex and increasing treatment difficulty.Currently,there are no established recommendations in China for the diagnosis and treatment of CVD in individuals aged 60 and above.Against this backdrop,the Peripheral Vascular Disease Management Branch of the Chinese Geriatric Society has developed the Chinese Expert Consensus on the Diagnosis and Treatment of Chronic Venous Disease in the Elderly based on domestic and international guidelines,relevant evidence-based medical research,and the physiological and clinical characteristics of the elderly population in China.This consensus aims to provide an important reference for improving the diagnosis and treatment of CVD in elderly patients in China.

BACKGROUND:The blood-brain barrier is an important structure that protects the central nervous system,and the study of the effects of high glucose on the blood-brain barrier is important for the prevention of high glucose-induced damage to the central nervous system.OBJECTIVE:To investigate the potential effect of high glucose on the blood-brain barrier function of hCMEC/D3 human brain microvascular endothelial cells.METHODS:hCMEC/D3 cells were cultured in regular sugar medium(glucose concentration of 25 mmol/L)and high-sugar medium(glucose concentration of 55 mmol/L).The morphology of cells in each group was observed by light microscopy.CCK-8 assay was used to detect changes in cell viability.A monolayer blood-brain barrier model was established using hCMEC/D3 cell line with Transwell chamber device.Changes in cell transmembrane resistance were monitored daily.The permeability of cell monolayers was detected by phenol red permeability.Flow cytometry was used to detect the apoptosis rate of the cells.Western blot assay was used to detect the expression of Bcl-2,Bax,Caspase-3,ZO-1,Occludin,Claudin-1,and histone deacetylase 4.The levels of histone deacetylase in cell supernatant were detected by ELISA.The expression of histone deacetylase 4 in cells was detected by immunofluorescence.RESULTS AND CONCLUSION:(1)The cell viability of high sugar group was significantly lower than that of control group(P＜0.000 1).(2)The cells of the control group were in a good growth state,interwoven into a dense mesh,with interconnections between synapses.The cell growth of high glucose group was suppressed,and the connection of inter-cellular synapses was reduced.(3)Compared with the control group,the transmembrane resistance value of the high glucose group was reduced(P＜0.05);phenol-red permeability of the monolayer cell membrane was increased(P＜0.05);cell apoptosis rate was increased(P＜0.01);the expression of Bax protein was increased(P＜0.000 1);the expression of Caspase-3 protein had no significant change(P＞0.05);the expression of Bcl-2,ZO-1,Occludin,Claudin-1,and histone deacetylase 4 proteins was decreased(P＜0.01,P＜0.001,P＜0.01,P＜0.000 1,P＜0.01);the fluorescence expression of histone deacetylase 4 was decreased(P＜0.001)in the high glucose group.(4)The level of histone deacetylase 4 in the cell supernatant of the high glucose group was lower than that of the control group(P＜0.05).The results show that high glucose induces the increased apoptosis and enhances permeability of hCEMCE/D3 cells,and its mechanism may be related to the decreased expression level of histone deacetylase 4.

Objective:To evaluate the characteristic manifestations of lumbar fusion following oblique lateral interbody fusion (OLIF), determine the specific incidence of these patterns, and the identify factors associated with fusion characteristics.Methods:This retrospective study analyzed 209 patients who underwent OLIF surgery at Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, between July 2017 and September 2023. The cohort had a mean age of 64.2±9.8 years and included 125 males and 84 females. A total of 338 lumbar segments were assessed, comprising 159 segments treated with stand-alone OLIF (OLIF-SA) and 179 segments treated with OLIF combined with posterior pedicle screw fixation (OLIF-PSF). Inclusion criteria were: patients aged 18-80 years who underwent OLIF with complete radiographic records. Surgical parameters, including fixation method, number of fused segments, surgical approach, and cage dimensions (height and width), were obtained from operative records. Radiographic evaluation included preoperative osteophytes, Hounsfield unit (HU) values of endplates, and cage positioning. Fusion rate, fusion pattern (lateral vs. central), cage subsidence, and related influencing factors were assessed. Clinical outcomes were measured via the Oswestry disability index (ODI) and visual analog scale (VAS) preoperatively, immediately postoperatively, and at 1-year follow-up. Results:The overall fusion rate was 98.2% (332/338), with a non-union rate of 1.8% (6/338). The incidence of lateral fusion was 40.2% (136/338). In the OLIF-SA group, lateral and central fusion rates were 50.3% (80/159) and 49.7% (79/159), respectively, with no cases of non-union. In the OLIF-PSF group, lateral fusion occurred in 31.3% (56/179), central fusion in 65.4% (117/179), and non-union in 3.3% (6/179), with statistically significant differences between groups ( P<0.05). Preoperative osteophytes and higher endplate HU values were significantly associated with lateral fusion ( P<0.05). However, cage dimensions and cage position (anterior-posterior and lateral placement) were not significantly associated with fusion pattern ( P>0.05). Overall, 61.5% (208/338) of segments showed no cage subsidence; 24.5% (83/338) had settling, and 14.0% (47/338) had grade 1 or higher subsidence. Among lateral fusion cases, the rates of no subsidence, anchoring, grade 1, grade 2, and grade 3 subsidence were 67.6%, 21.3%, 7.4%, 3.9%, and 0.7%, respectively. In the central fusion group, these rates were 59.2%, 27.6%, 9.2%, 2.5%, and 1.3%, respectively. In the non-union group, grade 2 and 3 subsidence occurred in 50% (3/6) each, significantly higher than in the other fusion groups ( P<0.05). Post hoc analysis confirmed that grade 2 and 3 subsidence rates were significantly elevated in the non-union group compared to the lateral and central fusion groups, while other subsidence categories showed no significant differences across groups. Clinically, patients showed significant improvements in ODI and VAS scores following surgery ( P<0.05). Conclusions:Lateral fusion occurred in 40.2% of OLIF cases. The OLIF-SA technique, preoperative osteophytes, and elevated preoperative HU values were significantly associated with lateral fusion. In contrast, surgical approach, number of fused segments, cage height, width, and cage positioning did not significantly influence the occurrence of lateral fusion.

China's Medical Service Price(MSP)reform has entered a new phase,implementing management measures.The compilation,implementation,and coordination of MSP item guidelines and the existing contradictions and problems were reviewed.It proposes strengthening price item management in planning under the background of the new era,itemizing in the alignment particle size,and comparing prices in the same coordinate system.This can offer systematic approaches and innovative strategies for improving the quality and efficiency of deepening MSP reform.

Objective:To evaluate the effectiveness and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with stage 4/M neuroblastoma (NB).Methods:This study was a prospective, single-arm, multicenter clinical trial conducted by Sun Yat-sen Memorial Hospital, Children′s Hospital of Nanjing Medical University, Children′s Hospital, Zhejiang University School of Medicine, the First Affiliated Hospital of Guangxi Medical University, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. From March, 2019 to August, 2023, 25 children with confirmed with stage 4/M NB and received allo-HSCT were enrolled. The patients received either unrelated cord blood transplantation (UCBT) or peripheral blood stem cell transplantation (PBSCT). Conditioning regimens for UCBT was fludarabine+busulfan+cyclophosphamide+topotecan, and for PBSCT was fludarabine+busulfan+melphalan+thiotepa+antithymocyte globulin, respectively. Until the last follow-up date of September, 2023, the overall survival (OS) rate and event free survival (EFS) rate were analyzed to evaluate efficacy. The engraftment rate and transplant-related complications were statistically assessed to evaluate safety. Survival analysis was performed using the Kaplan-Meier method.Results:Of the 25 patients, there were 15 males and 10 females. The age at transplantation was 5.7 (3.8, 7.3) years. The engraft rate was 100%, with recovery time of neutrophil as 15.7 (12.5, 17.0) d, and the recovery time of platelets as 33.5 (18.0, 48.0) d. Seventeen of the 25 children (68%) developed acute graft versus host disease (aGVHD), occurred at 18.0 (13.0, 22.5) d after transplantation, including 13 of grade Ⅲ-Ⅳ cases. The main sites of aGVHD were skin and intestinal tract. After treatment, 13 cases improved, 4 patients developed chronic graft-versus-host disease (cGVHD). After allo-HSCT, 14 children received maintenance therapy. Twenty of the 25 patients survived, the 2-year cumulative OS rate was (80±9)%, and 2-year EFS rate was (56±11)%. Nine cases (36%) relapsed, the time from allo-HSCT to disease relapse was 10.9 (5.5, 16.0) months. Five cases (20%) died. The hematopoietic stem cell transplantation associated mortality rate was 4% (1/25).The 2-year OS rate of patients who had partial remission prior to allo-HSCT was significant lower than those who had complete remission prior to allo-HSCT ((33±25)% vs. 100%, P=0.037). Conclusion:allo-HSCT is an effective treatment for patients with stage 4/M NB.

The underlying cause of low response rates to existing immunotherapies is that tumor cells dominate tumor immune escape through surface antigen deficiency and inducing tumor immunosuppressive microenvironment (TIME). Here, we proposed an in situ tumor cell engineering strategy to disrupt tumor immune escape at the root by restoring tumor cell MHC-I/tumor-specific antigen complex (MHC-I/TSA) expression to promote T-cell recognition and by silencing tumor cell CD55 to increase the ICOSL⁺ B-cell proportion and reverse the TIME. A doxorubicin (DOX) and dual-gene plasmid (MAC pDNA, encoding both MHC-I/ASMTNMELM and CD55-shRNA) coloaded drug delivery system (LCPN@ACD) with tumor targeting and charge/size dual-conversion properties was prepared. LCPN@ACD-induced ICD promoted DC maturation and enhanced T-cell activation and infiltration. LCPN@ACD enabled effective expression of MHC-I/TSA on tumor cells, increasing the ability of tumor cell recognition and killing. LCPN@ACD downregulated tumor cell CD55 expression, increased the proportion of ICOSL⁺ B cells and CTLs, and reversed the TIME, thus greatly improving the efficacy of αPD-1 and CAR-T therapies. The application of this in situ tumor cell engineering strategy eliminated the source of tumor immune escape, providing new ideas for solving the challenges of clinical immunotherapy.