Hepatocellular carcinoma(HCC)expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming.Aldolase A(ALDOA)plays a prominent role in glycolysis;however,little is known about its role in HCC development.In the present study,we aim to explore how ALDOA is involved in HCC proliferation.HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout,which is consistent with ALDOA overexpression encouraging HCC prolifera-tion.Mechanistically,ALDOA knockout partially limits the glycolytic flux in HCC cells.Meanwhile,ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase;ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function.A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun,and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells.In HCC patients,the expression level of ALDOA was correlated with the phosphorylation level of c-Jun(Thr93)and poor prognosis.Remarkably,hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models,and the knockdown of Aldoa strikingly decreased HCC development in vivo.Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription,opening additional avenues for anti-cancer therapies.

Spine fracture and dislocation are common traumatic spinal conditions that often require surgical intervention due to compromised spinal stability. Surgical approaches include anterior, posterior, and combined anterior-posterior spinal procedures. According to the specific surgical requirements, patients may be placed in the prone position or repositioned between prone and supine positions during surgery. Intraoperative repositioning has become an essential step in patient positioning. However, during repositioning, patients with spinal fracture and dislocation are at increased risk for complications such as hemodynamic instability, nerve injury, and pressure injuries to the skin and soft tissue. Notably, due to the instability of the spinal cord, even minor manipulations can further exacerbate the damage, potentially leading to severe outcomes like paraplegia. Although the current clinical guidelines provide instructive recommendations for standard position, there remains no specific protocols for intraoperative repositioning in patients with spine fracture and dislocation. With a concern for the lack of clinical studies on positioning techniques, risk prevention, and operational norms for special patients, no applicable guidelines or standards are available. A consensus was required to provide clinical reference, meet the requirements of surgical treatment, and minimize the safety risks of patients caused by improper placement of positions. Professional Committee of Operating Room Nursing of Shaanxi Nursing Association organized experts in nursing management and operating room nursing from major hospitals across China to formulate Expert consensus on intraoperative repositioning for patients with spinal fracture and dislocation ( version 2025). The consensus provides 11 recommendations covering pre-repositioning preparation, intraoperative maneuvers, and post-repositioning observation, aiming to provide references for clinical standardization of the intraoperative repositioning process and protection of patients′ safety.

Microglial pyroptosis and neuroinflammation have been implicated in the pathogenesis of sepsis-associated encephalopathy (SAE). OGT-mediated O-GlcNAcylation is involved in neurodevelopment and injury. However, its regulatory function in microglial pyroptosis and involvement in SAE remains unclear. In this study, we demonstrated that OGT deficiency augmented microglial pyroptosis and exacerbated secondary neuronal injury. Furthermore, OGT inhibition impaired cognitive function in healthy mice and accelerated the progression in SAE mice. Mechanistically, OGT-mediated O-GlcNAcylation of ATF2 at Ser44 inhibited its phosphorylation and nuclear translocation, thereby amplifying NLRP3 inflammasome activation and promoting inflammatory cytokine production in microglia in response to LPS/Nigericin stimulation. In conclusion, this study uncovers the critical role of OGT-mediated O-GlcNAcylation in modulating microglial activity through the regulation of ATF2 and thus protects against SAE progression.
Animals ; Microglia/metabolism* ; Pyroptosis/physiology* ; Mice ; Sepsis-Associated Encephalopathy/prevention & control* ; Activating Transcription Factor 2/metabolism* ; N-Acetylglucosaminyltransferases/genetics* ; Mice, Inbred C57BL ; Male ; Mice, Knockout

Hepatocellular carcinoma (HCC) expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming. Aldolase A (ALDOA) plays a prominent role in glycolysis; however, little is known about its role in HCC development. In the present study, we aim to explore how ALDOA is involved in HCC proliferation. HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout, which is consistent with ALDOA overexpression encouraging HCC proliferation. Mechanistically, ALDOA knockout partially limits the glycolytic flux in HCC cells. Meanwhile, ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase; ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function. A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun, and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells. In HCC patients, the expression level of ALDOA was correlated with the phosphorylation level of c-Jun (Thr93) and poor prognosis. Remarkably, hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models, and the knockdown of A ldoa strikingly decreased HCC development in vivo. Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription, opening additional avenues for anti-cancer therapies.

Spine fracture and dislocation are common traumatic spinal conditions that often require surgical intervention due to compromised spinal stability. Surgical approaches include anterior, posterior, and combined anterior-posterior spinal procedures. According to the specific surgical requirements, patients may be placed in the prone position or repositioned between prone and supine positions during surgery. Intraoperative repositioning has become an essential step in patient positioning. However, during repositioning, patients with spinal fracture and dislocation are at increased risk for complications such as hemodynamic instability, nerve injury, and pressure injuries to the skin and soft tissue. Notably, due to the instability of the spinal cord, even minor manipulations can further exacerbate the damage, potentially leading to severe outcomes like paraplegia. Although the current clinical guidelines provide instructive recommendations for standard position, there remains no specific protocols for intraoperative repositioning in patients with spine fracture and dislocation. With a concern for the lack of clinical studies on positioning techniques, risk prevention, and operational norms for special patients, no applicable guidelines or standards are available. A consensus was required to provide clinical reference, meet the requirements of surgical treatment, and minimize the safety risks of patients caused by improper placement of positions. Professional Committee of Operating Room Nursing of Shaanxi Nursing Association organized experts in nursing management and operating room nursing from major hospitals across China to formulate Expert consensus on intraoperative repositioning for patients with spinal fracture and dislocation ( version 2025). The consensus provides 11 recommendations covering pre-repositioning preparation, intraoperative maneuvers, and post-repositioning observation, aiming to provide references for clinical standardization of the intraoperative repositioning process and protection of patients′ safety.

Objective:To investigate effect of acacetin on alveolar epithelial cell damage caused by Streptococcus pneumoniae(SP)infection by regulating sirtuin 1(Sirt1)-mediated 5'-AMP activated protein kinase(AMPK)/nuclear factor erythroid-2 related factor 2(Nrf2)signaling pathway.Methods:Alveolar epithelial cells A549 cultured in vitro were infected with SP to establish a cell damage model.After treatment with acacetin at final concentrations of 0,5,25,50,100,150,200 μmol/L,CCK-8 was performed to detect cell viability of each treatment group and optimal concentration of acacetin was screened.A549 cells cultured in vitro were ran-domly separated into five groups:control group,model group,acacetin(150 μmol/L)group,EX527(Sirt1 inhibitor,40 μmol/L)group,acacetin(150 μmol/L)+EX527(40 μmol/L)group,control group was not treated,other groups were infected with SP to establish a cell damage model,and then treated with 150 μmol/L acacetin and 40 μmol/L EX527,CCK-8 and flow cytometry were performed to measure cell viability and apoptosis rate in each group;kits were performed to measure levels of reactive oxygen species(ROS),superoxide dismutase(SOD),malondialdehyde(MDA),lactate dehydrogenase(LDH)and IL-10,IL-1β,TNF-α levels of cells in each group;Western blot was performed to measure proliferation-related proteins Ki-67,proliferating cell nuclear antigen(PCNA),apoptosis-related proteins caspase-9,Bax,Sirt1 and AMPK/Nrf2 signaling pathway proteins p-AMPK/AMPK,Nrf2 expres-sions of cells in each group.Results:Model group had decreased A549 cell viability,SOD and IL-10 levels,p-AMPK/AMPK,Sirt1,Nrf2,Ki-67 and PCNA protein expressions(P<0.05),and increased apoptosis rate,MDA,LDH,ROS,IL-1β and TNF-α levels than control group(P<0.05).Compared with model group and acacetin+EX527 group,acacetin group had increased A549 cell viability,SOD and IL-10 levels,p-AMPK/AMPK,Sirt1,Nrf2,Ki-67 and PCNA protein expressions(P<0.05),and decreased apoptosis rate,MDA,LDH,ROS,IL-1β and TNF-α levels(P<0.05);EX527 group had decreased A549 cell viability,SOD and IL-10 levels,p-AMPK/AMPK,Sirt1,Nrf2,Ki-67 and PCNA protein expressions(P<0.05),and increased apoptosis rate,MDA,LDH,ROS,IL-1β and TNF-α levels(P<0.05).Conclusion:Acnestin can activate AMPK/Nrf2 signaling by up-regulating Sirt1 expression,thereby promoting secretion of anti-inflammatory factors,reducing production of ROS and pro-inflammatory factors,reducing inflammation and oxidative stress,and finally alleviating neuronal damage.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).

Objective:To investigate the effects of hyperbaric oxygen（HBO）combined with Temozolomide（TMZ）on the cell cycle and apoptosis of lung cancer A549 cells，and to study its mechanisms.Methods:After the cell culture，the human lung cancer A549 cells were divided into control group，HBO group，TMZ group，and HBO+TMZ group according to the experimental design，and were given，respectively，no treatment，50 μmol/L TMZ for 24 h，0.2 MPa HBO for 3 h，and 0.2 MPa HBO pretreatment for 3 h followed by 50 μmol/L TMZ for 24 h. The cell proliferation was detected by Cell Counting Kit-8（CCK-8）experiment；the cell apoptosis and cell cycle were detected by flow cytometry；the expression of AKT/mTOR signaling pathway proteins in A549 cells was detected by Western blotting.Results:The survival rate of A549 cells in the HBO+TMZ group was significantly lower than those of the other three groups（ P < 0.05 or P < 0.01）. The apoptosis rates in the control group，HBO group，TMZ group，and HBO+TMZ group were（6.73 ± 1.47）%，（8.52 ± 0.87）%，（32.78 ± 3.49）%，and（49.61 ± 5.74）%，respectively；the apoptosis rate in the HBO+TMZ group was significantly higher than those in the other three groups，and the differences were statistically significant（ P < 0.05）. The results of cell cycle experiment showed that the number of A549 cells in G2/M phase was increased in the HBO+TMZ group with a cell percentage of 35.81%，which was significantly higher than those of the other three groups（ P < 0.05）. The expression levels of p-AKT and mTOR proteins in A549 cells in the HBO+TMZ group were significantly lower than those in the other three groups（ P < 0.01）. Conclusion:The combination of HBO and TMZ can greatly improve the inhibition on the proliferation and induce apoptosis of lung cancer A549 cells，which is achieved by regulating the AKT/mTOR signaling pathway to block the A549 cells in the G2/M phase.

Objective:To investigate the effects of hyperbaric oxygen（HBO）combined with Temozolomide（TMZ）on the cell cycle and apoptosis of lung cancer A549 cells，and to study its mechanisms.Methods:After the cell culture，the human lung cancer A549 cells were divided into control group，HBO group，TMZ group，and HBO+TMZ group according to the experimental design，and were given，respectively，no treatment，50 μmol/L TMZ for 24 h，0.2 MPa HBO for 3 h，and 0.2 MPa HBO pretreatment for 3 h followed by 50 μmol/L TMZ for 24 h. The cell proliferation was detected by Cell Counting Kit-8（CCK-8）experiment；the cell apoptosis and cell cycle were detected by flow cytometry；the expression of AKT/mTOR signaling pathway proteins in A549 cells was detected by Western blotting.Results:The survival rate of A549 cells in the HBO+TMZ group was significantly lower than those of the other three groups（ P < 0.05 or P < 0.01）. The apoptosis rates in the control group，HBO group，TMZ group，and HBO+TMZ group were（6.73 ± 1.47）%，（8.52 ± 0.87）%，（32.78 ± 3.49）%，and（49.61 ± 5.74）%，respectively；the apoptosis rate in the HBO+TMZ group was significantly higher than those in the other three groups，and the differences were statistically significant（ P < 0.05）. The results of cell cycle experiment showed that the number of A549 cells in G2/M phase was increased in the HBO+TMZ group with a cell percentage of 35.81%，which was significantly higher than those of the other three groups（ P < 0.05）. The expression levels of p-AKT and mTOR proteins in A549 cells in the HBO+TMZ group were significantly lower than those in the other three groups（ P < 0.01）. Conclusion:The combination of HBO and TMZ can greatly improve the inhibition on the proliferation and induce apoptosis of lung cancer A549 cells，which is achieved by regulating the AKT/mTOR signaling pathway to block the A549 cells in the G2/M phase.

Objective:To observe the changes of the structure and visual function of the retina in patients with or without the ectopic inner foveal layers (EIFL) and to explore the factors influencing the recovery of visual function in patients with idiopathic epimacular membrane (IMEM).Methods:A retrospective clinical study. From March 2015 to June 2019, 90 patients with MEM who were diagnosed by Ophthalmic Center of the Second Hospital of Hebei Medical University were enrolled in the study. All patients were examined by best corrected visual acuity (BCVA) and frequency domain optical coherence scan. BCVA was recorded by Snellen vision table, and it was converted into the minimum resolution angle logarithm (logMAR) vision. Among 90 eyes, IMEM grade 2-4 was 68 (75.6%, 68/90), 18 (20.0%, 18/90), 4 (4.4%, 4/90), respectively. According to this, the grade 2 was set as group A, and the grade 3 and grade 4 were combined to group B. There was no significant difference in age ( t=0.015), sex composition ratio of patients between two groups ( χ2=0.060) and the average of central macular thickness (CMT) ( F=2.277) ( P=0.904, 0.809, 0.141). The difference of average logMAR and BCVA was statistically significant ( F=35.913, P=0.000). All patients underwent 25G pars plana three channel vitrectomy with simultaneous removal of epiretinal membrane and internal limiting membrane. BCVA, CMT and improvement of IMEM grading were observed at 1, 3, 6 and 12 months after operation. BCVA, EIFL thickness and CMT were compared before and after operation by single factor repeated variance analysis; Fisher exact probability method was used to compare the changes of the anatomical structure of the eyes in the two groups at 12 months after operation. Results:1, 3, 6, 12 months after operation, the average eyes of logMAR BCVA in group A were 0.50±0.13, 0.38±0.12, 0.27±0.12, 0.19±0.10. The patients in group B were 0.66±0.14, 0.60±0.13, 0.54±0.14, 0.52±0.14. CMT in group A were 364.82±81.29, 281.65±72.45, 228.55±55.34, 182.84±56.13 μm. The patients in group B were 455.88±69.60, 440.18±68.65, 383.76±65.38, 371.39±66.60 μm. The difference was statistically significant in the two groups (BCVA: F=37.913, 11.479, 24.250, 39.013; P=0.000, 0.002, 0.000, 0.000. CMT: F=10.987, 39.610, 55.789, 79.987; P=0.002, 0.000, 0.000, 0.000). In group A, IMEM was improved to 57 eyes of grade 1 on 12 months after operation. Among the 18 eyes in group B, IMEM was improved to 1 and 3 eyes in level 1 and level 2, respectively, and no improvement was found in 4 eyes in grade 4. The difference was statistically significant ( P=0.000) in the improvement of the number of eyes in the two groups. Conclusions:The patients with IMEM without EIFL have better visual prognosis and reversible anatomical changes. EIFL is an important factor affecting the visual function and anatomical structure recovery after operation.