Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Objective:To analyze the genetic characteristics of influenza B virus Victoria lineage in Ma′anshan from 2019 to 2022.Methods:Throat swabs were collect from cases with influenza-like illness in three sentinel hospitals and from influenza outbreak events in Ma′anshan city from 2019 to 2022. Real-time fluorescence-based PCR was performed to detect the nucleic acids of influenza viruses in the swab samples. Statistical analysis was conducted using the influenza year as the detection cycle. MDCK cells and chicken embryos were used for virus isolation, and 31 strains of B/Victoria lineage were selected for whole-genome sequencing and genetic analysis.Results:A total of 11 258 throat swabs were collected from ILI cases, and 8.90% (1 002/11 258) of them tested positive for B/Victoria. Except for the period from the winter of 2020 to the spring of 2021, during which no epidemic outbreak of influenza was observed, there were peaks in the prevalence of B/Victoria influenza in winter and spring of the other years, with the positive rates ranging from 12.65% (54/427) to 46.68% (176/377) during peak seasons. Compared with the recommended vaccine strains, the homology of the HA gene nucleotides of the viral strains isolated from 2019 to 2022 ranged from 98.40% to 99.26%, and the homology of amino acids ranged from 96.21% to 98.80%. All isolated strains carried mutations in the 190-helix of the hemagglutinin protein; the strains isolated from 2019 to 2020 had two amino acid insertions at position 160-loop; and the strains isolated from 2021 and 2022 had mutations at positions 120-loop and 150-loop. No drug-resistant mutations were detected in the neuraminidase gene.Conclusions:The B/Victoria strains isolated in Ma′anshan city from 2019 to 2022 have key site variations as compared with the recommended vaccine strains, suggesting a decrease in vaccine immune efficacy. Therefore, it is necessary to strengthen the surveillance of viral mutations to provide reference for updating vaccine strains and formulating epidemic prevention and control measures.

BACKGROUND:Rev-erbα is involved in the regulation of inflammation,but pharmacological activation of Rev-erbα increases the risk for cardiovascular diseases.To reduce the relevant risk,an exploration on SR9009,a Rev-erbα agonist,combined with other drugs to relieve inflammation in skeletal myoblasts was conducted,laying the theoretical foundation for the treatment of inflammation-associated skeletal muscle atrophy. OBJECTIVE:To investigate the relationship of SR9009,indolepropionic acid and nuclear factor-κB signaling pathways in lipopolysaccharide-induced C2C12 myoblasts. METHODS:(1)C2C12 myoblasts were induced to differentiate in the presence of lipopolysaccharide(1 μg/mL).RNA-seq and KEGG pathway analysis were used to study signaling pathways.(2)C2C12 myoblast viability was assessed using the cell counting kit-8 assay to determine optimal concentrations of indolepropionic acid.Subsequently,cells were categorized into control group,lipopolysaccharide(1 μg/mL)group,SR9009(10 μmol/L)+lipopolysaccharide group,indolepropionic acid(80μmol/L)+lipopolysaccharide group,and SR9009+indolepropionic acid+lipopolysaccharide group.ELISA was employed to measure protein expression levels of interleukin-6 in the cultured supernatant.Real-time quantitative PCR were employed to measure mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Western blot assay were employed to measure protein expression levels of NF-κB p65 and p-NF-κB p65.(3)After Rev-erbα was knocked down by siRNA,knockdown efficiency was assessed by RT-qPCR.And mRNA levels of interleukin-6 and tumor necrosis factor α were also measured. RESULTS AND CONCLUSION:Compared with the blank control group,lipopolysaccharide time-dependently inhibited myofibroblast fusion to form myotubes,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were elevated,and the level of interleukin-6 in the cell supernatant was significantly increased.The results of KEGG pathway showed that the nuclear factor-κB signaling pathway was activated by lipopolysaccharide.Indolepropionic acid exhibited significant suppression of C2C12 myoblasts viability when its concentration exceeded 80 μmol/L.Indolepropionic acid and SR9009 inhibited the activation of NF-κB signaling pathway,thereby played an anti-inflammatory role,and suppressed the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Compared with the lipopolysaccharide group,the ratio of p-NF-κB p65/NF-κB p65 protein expression were downregulated.SR9009 combined with indolepropionic acid notably reduced lipopolysaccharide-induced inflammation,further downregulated the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.The ratio of p-NF-κB p65/NF-κB p65 protein expression was significantly lower than that in the SR9009+lipopolysaccharide group or indolepropionic acid+lipopolysaccharide group.Rev-erbα increases time-dependently with lipopolysaccharide induction.The knockdown efficiency of Rev-erbα by siRNA reached over 58%,and lipopolysaccharide was added after Rev-erbα was successfully knocked down.Compared with the lipopolysaccharide group,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were significantly up-regulated.These results conclude that Rev-erbα may act as a promising pharmacological target to reduce inflammation.SR9009 targeted activation of Rev-erbα combined with indolepropionic acid significantly inhibits the nuclear factor-κB signaling pathway and attenuates the inflammatory response of C2C12 myofibroblasts.Moreover,the combined anti-inflammatory effect is superior to that of the intervention alone.

BACKGROUND:For thoracolumbar spine fractures with developmental stenosis of the vertebral arch,accurate nail placement is difficult using traditional fluoroscopy-assisted techniques.O-arm navigation assistance systems offer higher precision in general vertebral arch nail placement,but there is scarce literature on the application of O-arm navigation-assisted nail placement in thoracolumbar spine fractures with developmental stenosis of the vertebral arch both domestically and abroad. OBJECTIVE:To explore the accuracy of percutaneous vertebral arch nail placement assisted by O-arm navigation in patients with thoracolumbar spine fractures complicated by developmental stenosis of the vertebral arch. METHODS:A retrospective analysis was conducted on 53 patients who underwent percutaneous vertebral arch screw fixation surgery at Department of Orthopedics,General Hospital of Central Theater Command of PLA for thoracolumbar spine fractures complicated by developmental stenosis of the vertebral arch from January 2021 to March 2023.Totally 208 cases of vertebral arch developmental stenosis were found(cases with multiple vertebral arch developmental stenosis were counted separately).Based on the surgical approach,the patients were divided into two groups:O-arm navigation group(n=98)and C-arm fluoroscopy group(n=110).Postoperative imaging data were compared between the two groups,including anatomical perforation score,functional perforation score,actual vs.expected nail trajectory in the horizontal plane,and sagittal plane angle differences. RESULTS AND CONCLUSION:(1)There was no significant difference in the narrowest width of the pedicle isthmus(pow)between the two groups of patients(P>0.05).The proportions of different degrees of narrowing(mild:6 mm≤pow<7 mm,moderate:5 mm≤pow<6 mm,severe:pow<5 mm)were also not significantly different between the two groups(P>0.05).(2)The overall grade and scores of anatomical perforation and functional perforation were lower in the O-arm group compared to the C-arm group,and these differences were statistically significant(P<0.001).In terms of the angular deviation between the actual and planned screw trajectories,the O-arm group had smaller deviations,and these differences were statistically significant(P<0.05).(3)In the mild and moderate narrowing groups,the O-arm group showed significant advantages in anatomical perforation,functional perforation,and angular deviation between actual and planned screw trajectories,and these differences were statistically significant(P<0.001).(4)The O-arm group demonstrated better performance in anatomical perforation and functional perforation,especially in the T12-L2 segment,with more significant advantages.Additionally,the O-arm group had better angular deviations in actual and planned screw trajectories in all segments compared to the C-arm group.(5)Therefore,the use of O-arm navigation-assisted percutaneous screw placement for the treatment of thoracolumbar fractures with developmental pedicle isthmal narrowing provides higher accuracy and safer surgery.

Objective: To construct and validate a prognostic model for lung cancer based on acrolein-related genes using bioinformatics methods . Methods: Lung cancer datasets GSE30219 and GSE68465 were obtained from the GEO database , and acrolein-related gene sets were retrieved from the CTD database . Differentially expressed genes (DEGs) between cancer and adjacent tissues were identified in the GSE30219 dataset. The intersection of these DEGs and acrolein-related genes was then used to identify candidate genes . Gene set variation analysis ( GSVA) was performed to assess functional alterations based on the intersection genes . A protein-protein interaction (PPI) network was constructed based on the STRING database to identify core hub genes . Subsequently , support vector machine recursive feature elimination (SVM-RFE) and LASSO-Cox regression analyses were employed to develop a prognostic model based on acrolein-related genes , which was independently validated using the GSE68465 dataset. The CIBERSORT algorithm was applied to evaluate the immune cell infiltration characteristics between high- and low-risk groups , and functional enrichment analysis of DEGs between the two groups was conducted to further ex- plore the potential molecular mechanisms underlying the prognostic model . Results : A total of 361 acrolein-related DEGs were identified in lung cancer , and 7 key genes were selected for model construction . Kaplan-Meier survival analysis revealed that patients in the high-risk group had significantly lower survival rates compared to those in the low-risk group (P < 0. 000 1) . Receiver operating characteristic (ROC) curve analysis demonstrated that the mod- el possessed good predictive performance . Moreover , immune infiltration analysis indicated that the risk score was closely associated with multiple immune cell subsets , suggesting a potential role of acrolein-related genes in modula- ting the lung cancer immune microenvironment. Conclusion The prognostic model for lung cancer based on acro- lein-related genes demonstrates significant application value in predicting the prognosis of lung cancer , providing new insights into the potential mechanisms of acrolein in the onset and progression of lung cancer.

Objective To investigate the independent risk factors affecting the prognosis of chronic active antibody-mediated rejection (caAMR) after kidney transplantation. Methods A retrospective analysis was conducted on 61 patients who underwent renal biopsy and were diagnosed with caAMR. The patients were divided into caAMR group (n=41) and caAMR+TCMR group (n=20) based on the presence or absence of concurrent acute T cell-mediated rejection (TCMR). The patients were followed up for 3 years. The value of 24-hour urinary protein and estimated glomerular filtration rate (eGFR) at the time of biopsy in predicting graft loss was assessed using receiver operating characteristic (ROC) curves. The independent risk factors affecting caAMR prognosis were analyzed using the LASSO-Cox regression model. The correlation between grouping, outcomes, and Banff scores was compared using Spearman rank correlation matrix analysis. Kaplan-Meier analysis was used to evaluate the renal allograft survival rates of each subgroup. Results The 3-year renal allograft survival rates for the caAMR group and the caAMR+TCMR group were 83% and 79%, respectively. The area under the ROC curve (AUC) for predicting 3-year renal allograft loss was 0.83 ［95% confidence interval (CI) 0.70-0.97］ for eGFR and 0.78 (95% CI 0.61-0.96) for 24-hour urinary protein at the time of biopsy. LASSO-Cox regression analysis and Kaplan-Meier analysis showed that eGFR≤25.23 mL/(min·1.73 m²) and the presence of donor-specific antibody (DSA) against human leukocyte antigen (HLA) class I might be independent risk factors affecting renal allograft prognosis, with hazard ratios of 7.67 (95% CI 2.18-27.02) and 5.13 (95% CI 1.33-19.80), respectively. A strong correlation was found between the Banff chronic lesion indicators of renal interstitial fibrosis and tubular atrophy (P<0.05). Conclusions The presence of HLA class I DSA and eGFR≤25.23 mL/(min·1.73 m²) at the time of biopsy may be independent risk factors affecting the prognosis of caAMR.

Objective:To explore the diagnostic value of contrast-enhanced ultrasound (CEUS) combined with vimentin (VIM) and carbohydrate antigen 19-9 (CA19-9) for hilar cholangiocarcinoma (HCCA).Methods:A retrospective analysis was conducted on the case data of patients with HCCA and inflammatory pseudotumor of the liver admitted to Liaocheng People′s Hospital from June 2019 to June 2022. Among them, 68 patients with HCCA who underwent radical surgical resection were the observation group, and 60 patients with inflammatory pseudotumor of the liver were the control group. All patients underwent CEUS examination before the operation. The results of ultrasound manifestations were analyzed, and the levels of tissue VIM and serum CA19-9 in the two groups were compared. The relationship between tissue VIM, serum CA19-9 levels and the clinicopathological characteristics of patients with HCCA was analyzed. The receiver operating characteristic (ROC) curve was used to evaluate the value of CEUS parameters, tissue VIM and serum CA19-9 levels in the diagnosis of HCCA.Results:Among the 68 patients with HCCA, " fast in and fast out" was presented in CEUS. The numbers of cases with high enhancement, equal enhancement and low enhancement in the arterial phase were 47(69.12%), 16(23.53%) and 5(7.35%), respectively. The numbers of cases with low enhancement and equal enhancement in the portal vein stage were 53 cases (77.94%) and 15 cases (22.06%), respectively. All 68 cases (100%) in the delay period were of low enhancement. The proportions of patients with peripheral annular enhancement, overall heterogeneous enhancement and overall uniform enhancement in 60 cases of liver inflammatory pseudotumor were 20.00%(12/60), 40.00%(24/60) and 40.00%(24/60), respectively. There was no statistically significant difference in the time of initial enhancement between the two groups ( P>0.05). The peak time, isoenhancement time and the time of initial regression in the observation group were all longer than those in the control group (all P<0.05). The positive rate of VIM and the level of serum CA19-9 in the observation group were both higher than those in the control group (all P<0.05). The expression of VIM in the tissues of HCCA patients was related to tumor size, degree of differentiation, vascular invasion, lymph node metastasis and tumor node metastasis (TNM) stage (all P<0.05), but not related to nerve invasion ( P>0.05). The level of serum CA19-9 was related to tumor size, degree of differentiation, vascular invasion, nerve invasion, lymph node metastasis and TNM stage (all P<0.05). The results of the ROC curve showed that the combined detection of each parameter of CEUS (time to peak, time to start fading, time to equal enhancement) with VIM expression and serum CA19-9 level had a higher diagnostic efficacy for HCCA than the individual detection of each index. Conclusions:CEUS parameters, tissue VIM expression and serum CA19-9 all have certain diagnostic values for HCCA, and the combined detection has higher diagnostic efficacy.

Objective:To explore the diagnostic value of contrast-enhanced ultrasound (CEUS) combined with vimentin (VIM) and carbohydrate antigen 19-9 (CA19-9) for hilar cholangiocarcinoma (HCCA).Methods:A retrospective analysis was conducted on the case data of patients with HCCA and inflammatory pseudotumor of the liver admitted to Liaocheng People′s Hospital from June 2019 to June 2022. Among them, 68 patients with HCCA who underwent radical surgical resection were the observation group, and 60 patients with inflammatory pseudotumor of the liver were the control group. All patients underwent CEUS examination before the operation. The results of ultrasound manifestations were analyzed, and the levels of tissue VIM and serum CA19-9 in the two groups were compared. The relationship between tissue VIM, serum CA19-9 levels and the clinicopathological characteristics of patients with HCCA was analyzed. The receiver operating characteristic (ROC) curve was used to evaluate the value of CEUS parameters, tissue VIM and serum CA19-9 levels in the diagnosis of HCCA.Results:Among the 68 patients with HCCA, " fast in and fast out" was presented in CEUS. The numbers of cases with high enhancement, equal enhancement and low enhancement in the arterial phase were 47(69.12%), 16(23.53%) and 5(7.35%), respectively. The numbers of cases with low enhancement and equal enhancement in the portal vein stage were 53 cases (77.94%) and 15 cases (22.06%), respectively. All 68 cases (100%) in the delay period were of low enhancement. The proportions of patients with peripheral annular enhancement, overall heterogeneous enhancement and overall uniform enhancement in 60 cases of liver inflammatory pseudotumor were 20.00%(12/60), 40.00%(24/60) and 40.00%(24/60), respectively. There was no statistically significant difference in the time of initial enhancement between the two groups ( P>0.05). The peak time, isoenhancement time and the time of initial regression in the observation group were all longer than those in the control group (all P<0.05). The positive rate of VIM and the level of serum CA19-9 in the observation group were both higher than those in the control group (all P<0.05). The expression of VIM in the tissues of HCCA patients was related to tumor size, degree of differentiation, vascular invasion, lymph node metastasis and tumor node metastasis (TNM) stage (all P<0.05), but not related to nerve invasion ( P>0.05). The level of serum CA19-9 was related to tumor size, degree of differentiation, vascular invasion, nerve invasion, lymph node metastasis and TNM stage (all P<0.05). The results of the ROC curve showed that the combined detection of each parameter of CEUS (time to peak, time to start fading, time to equal enhancement) with VIM expression and serum CA19-9 level had a higher diagnostic efficacy for HCCA than the individual detection of each index. Conclusions:CEUS parameters, tissue VIM expression and serum CA19-9 all have certain diagnostic values for HCCA, and the combined detection has higher diagnostic efficacy.

Objective:To analyze the genetic characteristics of influenza B virus Victoria lineage in Ma′anshan from 2019 to 2022.Methods:Throat swabs were collect from cases with influenza-like illness in three sentinel hospitals and from influenza outbreak events in Ma′anshan city from 2019 to 2022. Real-time fluorescence-based PCR was performed to detect the nucleic acids of influenza viruses in the swab samples. Statistical analysis was conducted using the influenza year as the detection cycle. MDCK cells and chicken embryos were used for virus isolation, and 31 strains of B/Victoria lineage were selected for whole-genome sequencing and genetic analysis.Results:A total of 11 258 throat swabs were collected from ILI cases, and 8.90% (1 002/11 258) of them tested positive for B/Victoria. Except for the period from the winter of 2020 to the spring of 2021, during which no epidemic outbreak of influenza was observed, there were peaks in the prevalence of B/Victoria influenza in winter and spring of the other years, with the positive rates ranging from 12.65% (54/427) to 46.68% (176/377) during peak seasons. Compared with the recommended vaccine strains, the homology of the HA gene nucleotides of the viral strains isolated from 2019 to 2022 ranged from 98.40% to 99.26%, and the homology of amino acids ranged from 96.21% to 98.80%. All isolated strains carried mutations in the 190-helix of the hemagglutinin protein; the strains isolated from 2019 to 2020 had two amino acid insertions at position 160-loop; and the strains isolated from 2021 and 2022 had mutations at positions 120-loop and 150-loop. No drug-resistant mutations were detected in the neuraminidase gene.Conclusions:The B/Victoria strains isolated in Ma′anshan city from 2019 to 2022 have key site variations as compared with the recommended vaccine strains, suggesting a decrease in vaccine immune efficacy. Therefore, it is necessary to strengthen the surveillance of viral mutations to provide reference for updating vaccine strains and formulating epidemic prevention and control measures.

Objective:To evaluate the posterior fixation with inclined-long pedicle screws for the injured vertebra combined with two-level interbody fusion for thoracolumbar burst fractures with severe disc injury.Methods:A retrospective study was conducted to analyze the clinical data of 22 patients who had been treated for thoracolumbar burst fractures with severe disc injury at Department of Orthopaedic, General Hospital of Central Theater Command from June 2016 to June 2021. There were 15 males and 7 females, aged 43.50 (29.75, 52.25) years. By the AO classification, there were 12 cases of type B2, 10 cases of type C3. All the patients were treated by the posterior fixation with inclined-long pedicle screws for the injured vertebra combined with two-level interbody fusion. The visual analogue scale (VAS), Oswestry disability index (ODI), anterior vertebral height ratio (AVHR), kyphosis Cobb angle (KCA), vertebral wedge angle (VWA) and spinal canal encroachment rate (SCER) were compared between pre-surgery, 1 week post-surgery, 3 months post-surgery and the last follow-up. Their neurological function was graded according to the American Spinal Injury Association (ASIA) impairment scale and interbody fusion evaluated according to their 3D CT at the last follow-up.Results:All the 22 patients were followed up for (26.1±1.3) months. In all patients, the VAS and ODI were significantly lower at 1 week post-surgery than the pre-surgery ones ( P<0.05), and then decreased significantly at 3 months post-surgery and at the last follow-up compared with the values at 1 week post-surgery ( P<0.05). For all patients, there were significant improvements in AVHR, KCA, VWA and SCER at 1 week post-surgery, 3 months post-surgery and the last follow-up compared with the pre-surgery values ( P<0.05), and the SCER at the last follow-up was significantly decreased compared with that at 1 week post-surgery ( P<0.05). All patients experienced improved neurological function in different degrees at the last follow-up, and all intervertebral spaces achieved solid bony fusion. Conclusion:In the treatment of thoracolumbar burst fractures with severe disc injury, the posterior fixation with inclined-long pedicle screws for the injured vertebra combined with two-level interbody fusion can lead to satisfactory long-term therapeutic efficacy, because this strategy can effectively reduce spinal canal encroachment, restore the height of the injured vertebra, reconstruct the curvature of the fracture area and ensure reliable intervertebral fusion.