Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality, characterized by poor prognosis due to its high proliferative and invasive potential. Tumor metabolic reprogramming, particularly involving glucose metabolism, is essential for tumor survival. This study investigates the role of the Hippo pathway effector transcriptional co-activator with PDZ-binding motif (TAZ) in regulating gluconeogenesis and promoting tumorigenesis in HCC. Methods: TAZ expression in HCC was analyzed using The Cancer Genome Atlas data and validated in clinical samples and cell lines. TAZ was overexpressed or silenced in HCC cell lines to evaluate its effects on cell proliferation, apoptosis, migration, and invasion. The expression and prognostic relevance of the gluconeogenesis-related genes phosphoenolpyruvate carboxykinase 1 (PCK1) and glucose-6-phosphatase (G6PC) were examined, along with their correlation with TAZ expression. Tumor growth was assessed in nude mice. Interactions between TAZ and the glucocorticoid receptor (GR) were investigated using co-immunoprecipitation, immunofluorescence, and chromatin immunoprecipitation assays. Results: TAZ was significantly upregulated in HCC tissues and cell lines. TAZ overexpression enhanced proliferation, reduced apoptosis, and promoted migration and invasion. In contrast, PCK1 and G6PC were downregulated in HCC and showed a negative correlation with TAZ expression. Conclusion TAZ modulates gluconeogenesis and accelerates tumor growth, whereas its knockdown attenuates tumor progression. TAZ interacts with GR, suppressing its transcriptional activity on gluconeogenic gene promoters.

Objective To explore the role of SLIT-ROBO Rho GTPase-activating protein 2(srGAP2)in spinal motor neuron degeneration in amyotrophic lateral sclerosis(ALS).Methods Applied bioinformatics analysis to investigate the expression changes of srGAP2 in the spinal cord of human superoxide dismutase 1(hSOD1)mutant ALS transgenic mice.hSOD1 G93A mutant ALS transgenic mice were selected for animal experimental validation,with littermate wild type(WT)mice serving as the control group.A total of 36 pairs were divided into four groups,namely the pre-onset stage,early-onset stage,mid-onset stage,and late-onset stage.The expression changes and cellular localization of srGAP2 in the spinal cord of ALS mice were detected by Real-time PCR,Western blotting and immunofluorescent double-label staining.The hSOD1G93A mutant NSC34 motor neuron-like cell model was established,and in vitro experiments were carried out to detect the changes in srGAP2 expression,and the effects of srGAP2 over-expression on the viability of hSOD1G93A mutant NSC34 cells and the growth of cell protrusions.Results Bioinformatics analysis revealed abnormally low expression of srGAP2 in the spinal cord of hSOD1 mutant ALS mice.Animal experiments verified that compared with the WT mice,the expression of srGAP2 was reduced at both mRNA level and protein level in the spinal cord of hSOD1G93A mutant ALS transgenic mice at early-onset,mid-onset and late-onset stages.Compared with the WT mice,srGAP2 integral absorbance(IA)values in srGAP2+/NeuN+double-positive cells in the anterior horn of the spinal cord of hSOD1G93A mutant ALS transgenic mice were lower,srGAP2 IA values in srGAP2+/GFAP+double-positive cells were higher;Compared with the hSOD1WT NSC34 cells,the expression of srGAP2 was reduced at both mRNA level and protein level in hSOD1G93A mutant NSC34 cells.Over-expression of srGAP2 elevated the viability of hSOD1G93A mutant NSC34 cells,and up-regulated the expression level of synapse-related protein β Ⅲ-tubulin and growth associated protein 43(GAP43).Conclusion Low expression of srGAP2 is closely associated with the progression of ALS,while over-expression of srGAP2 can promote outgrowth of cell protrusions and exert a protective effect on spinal motor neurons in ALS.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

Hot melt extrusion(HME)technology employs thermodynamic and kinetic principles to mix pharmaceutical polymers with crystalline drugs at high temperatures and extrude them,embedding drug molecules within the polymer matrix to form solid dispersions.Due to its solvent-free nature,capability for one-step processing,and support for continuous operation,HME has garnered significant attention in the pharmaceutical industry in recent years.This article introduced the basic principles and development history of HME technology and its marketed drugs.It reviewed the research progress of HME technology in improving drug solubility,masking taste,controlled release,targeted release,oral dispersible films,implant formulations,semi-solid formulations,and 3D printed formulations.Additionally,the article summarized the advantages and limitations of HME technology and provided an outlook on its future development.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

Hot melt extrusion(HME)technology employs thermodynamic and kinetic principles to mix pharmaceutical polymers with crystalline drugs at high temperatures and extrude them,embedding drug molecules within the polymer matrix to form solid dispersions.Due to its solvent-free nature,capability for one-step processing,and support for continuous operation,HME has garnered significant attention in the pharmaceutical industry in recent years.This article introduced the basic principles and development history of HME technology and its marketed drugs.It reviewed the research progress of HME technology in improving drug solubility,masking taste,controlled release,targeted release,oral dispersible films,implant formulations,semi-solid formulations,and 3D printed formulations.Additionally,the article summarized the advantages and limitations of HME technology and provided an outlook on its future development.

Objective:To observe the short-and mid-term efficacy of left subclavian artery(LSA) laser in situ fenestration combined with arch debranching surgery for aortic arch reconstruction in patients with Stanford type A aortic dissection aged 60 years and above. Methods:This is a retrospective cohort study. A total of 41 Stanford type A aortic dissection patients aged 60 years and above who received combined surgery in Department of Endovascular Surgery, the First Affiliated Hospital of Zhengzhou University from January 2018 to December 2020 were retrospectively analyzed. There were 25 males and 16 females, aged (67.3±5.9)years(range: 60 to 75 years). Among them, 19 patients underwent LSA laser in situ fenestration combined with arch debranching surgery(combined surgery group) and 22 patients underwent hybrid aortic arch debranching surgery(non-combined surgery group). Independent sample t test, χ2 test and Fisher exact probability method were used to compare the clinical characteristics of the two groups. Kaplan-Meier method was used for survival analysis, and the 5-year survival rate of the two groups was compared by Log-rank test. Results:Body mass index in the combined operation group was significantly higher than that in the non-combined operation group ((27.1±1.6)kg/m 2vs.(26.9±1.9)kg/m 2; t=2.766, P=0.006), and the difference was statistically significant. There was no statistical significance in the comparison of other general data (all P>0.05). The operation time ((321.3±11.4) minutes vs. (329.6±7.3)minutes; t=-2.733, P=0.010) and LSA reconstruction time ((32.4±3.0)minutes vs. (42.4±6.0)minutes; t=-6.842, P<0.01) in the combined operation group were significantly shortened, and the difference was statistically significant. The rate of LSA reconstruction in the combined operation group (100% vs. 72.7%; P=0.023) was significantly higher than that in the non-combined operation group, and the difference was statistically significant. There were no significant differences in the incidence of pulmonary infection, unplanned second operation, continuous renal replacement therapy, neurological complications and the in-hospital mortality between the two groups. Compared with the non-combined surgery group, the total complication rate related to LSA reconstruction was significantly lower in the combined surgery group (0 vs. 27.3%; P=0.023). Kaplan-Meier survival analysis showed that there was no difference in 5-year survival rate between the combined operation group and the non-combined operation group (84.2% vs. 77.3%; χ2=0.310, P=0.578). Conclusion:Laser in situ fenestration of the LSA combined with arch debranching surgery to reconstruct the aortic arch can significantly shorten the operation and LSA reconstruction time in patients aged 60 years and above with Stanford type A aortic dissection, improve the success rate of LSA reconstruction, and reduce the occurrence rate of LSA reconstruction complications.

Objective To compare the biomechanical properties of new type of unicortical and unilateral external fixators by finite element analysis.Methods Firstly,a tibia model was reconstructed based on the CT data images using Mimics software,and then processed and modified by Geomagic Wrap software.Secondly,Solidworks software was used to establish the 3D models for new type of unicortical and unilateral external fixators,and fracture defect was made in the tibia model and then the model was assembled with the external fixators.Finally,mesh delineation was performed using ABAQUS software,and axial compression,torsion and bending loads were applied to the assemblies,respectively,to observe the stress distributions and fracture displacements and to evaluate the biomechanical properties of the 2 types of external fixators.Results The new type of unicortical external fixator had the mean and maximum stresses at the nail-bone interface and the stress distribution at the pin-bone contact surface lower than those of the unilateral external fixator under the three different loads,which behaved better in torsional resistance while worse in axial compression and bending resistance than the unilateral external fixator.Conclusion The new type of unicortical external fixator has the biomechanical stability slightly weaker than that of the unilateral external fixator,which shows sufficient stability and reasonable load distribution when used for temporary fixation with lower likelihood of nail breaking,periprosthetic fractures of the tibia pin tract and loosening of the bone pins when compared with the unilateral external fixator.[Chinese Medical Equipment Journal,2024,45(11):32-38]

The working principle of the optical system of Elekta Versa HD Linear Accelerator Agility head was introduced in brief.The causes for its daily failures were analyzed,and the countermeasures were put forward accordingly.References were provided for clinical engineers to treat similar failures.[Chinese Medical Equipment Journal,2024,45(7):118-120]

Objective:To observe the short-and mid-term efficacy of left subclavian artery(LSA) laser in situ fenestration combined with arch debranching surgery for aortic arch reconstruction in patients with Stanford type A aortic dissection aged 60 years and above. Methods:This is a retrospective cohort study. A total of 41 Stanford type A aortic dissection patients aged 60 years and above who received combined surgery in Department of Endovascular Surgery, the First Affiliated Hospital of Zhengzhou University from January 2018 to December 2020 were retrospectively analyzed. There were 25 males and 16 females, aged (67.3±5.9)years(range: 60 to 75 years). Among them, 19 patients underwent LSA laser in situ fenestration combined with arch debranching surgery(combined surgery group) and 22 patients underwent hybrid aortic arch debranching surgery(non-combined surgery group). Independent sample t test, χ2 test and Fisher exact probability method were used to compare the clinical characteristics of the two groups. Kaplan-Meier method was used for survival analysis, and the 5-year survival rate of the two groups was compared by Log-rank test. Results:Body mass index in the combined operation group was significantly higher than that in the non-combined operation group ((27.1±1.6)kg/m 2vs.(26.9±1.9)kg/m 2; t=2.766, P=0.006), and the difference was statistically significant. There was no statistical significance in the comparison of other general data (all P>0.05). The operation time ((321.3±11.4) minutes vs. (329.6±7.3)minutes; t=-2.733, P=0.010) and LSA reconstruction time ((32.4±3.0)minutes vs. (42.4±6.0)minutes; t=-6.842, P<0.01) in the combined operation group were significantly shortened, and the difference was statistically significant. The rate of LSA reconstruction in the combined operation group (100% vs. 72.7%; P=0.023) was significantly higher than that in the non-combined operation group, and the difference was statistically significant. There were no significant differences in the incidence of pulmonary infection, unplanned second operation, continuous renal replacement therapy, neurological complications and the in-hospital mortality between the two groups. Compared with the non-combined surgery group, the total complication rate related to LSA reconstruction was significantly lower in the combined surgery group (0 vs. 27.3%; P=0.023). Kaplan-Meier survival analysis showed that there was no difference in 5-year survival rate between the combined operation group and the non-combined operation group (84.2% vs. 77.3%; χ2=0.310, P=0.578). Conclusion:Laser in situ fenestration of the LSA combined with arch debranching surgery to reconstruct the aortic arch can significantly shorten the operation and LSA reconstruction time in patients aged 60 years and above with Stanford type A aortic dissection, improve the success rate of LSA reconstruction, and reduce the occurrence rate of LSA reconstruction complications.