Objective To explore the mechanism of Jiawei Jisheng Shenqi Decoction in improving the hypoxic microenvironment and antagonizing liver cirrhosis.Methods In vivo experiments were conducted using a rat model of carbon tetrachloride(CCL4)-induced liver cirrhosis.Rats were divided into normal,model,colchicine,JWJSSQ low-dose,JWJSSQ medium-dose,and JWJSSQ high-dose group.Pathological changes in liver tissues in each group were examined by hematoxylin and eosin(HE)and Masson staining,changes in serum liver function were detected using test kits,levels of hyaluronic acid(HA),laminin(LN),procollagen Ⅲ(PC Ⅲ),and collagen typeⅣ(COL4)were detected by enzyme-linked immunosorbent assay(ELISA),and protein expression levels of hypoxia-inducible factor-1α(HIF-1α),Notch1,Jagged1,and α-smooth muscle actin(α-SMA)were detected by Western blot.In vitro experiments were conducted in HSC-T6 cells,and the optimal concentration of CoCl2(100 μ mol/L,200μmol/L,400 μmol/L,600 μmol/L and 800 μmol/L)in the cultured cells and the optimal concentration of drug-containing serum(5％,10％,15％,20％)were determined by Cell Counting Kit-8(CCK-8)assay.The migration ability of cells in each group was detected by scratch testing,and changes in the apoptosis rates were determined by flow cytometry.Protein expression levels of HIF-1α,Notch1,Jagged1,α-SMA,matrix metallopeptidase 9(MMP9),and tissue inhibitor of metalloproteinases 1(TIMP-1)were detected by Western blot.Results In the in vivo experiments,liver swelling,inflammatory cell infiltration,collagen deposition,and the appearance of pseudolobules were significantly increased in the model group compared with those in the normal group.Serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),HA,LN,PCⅢ,and COL4 were significantly increased and albumin(ALB)was significantly decreased in the model group,while liver levels of HIF-1α,Notch1,Jagged1,and α-SMA proteins were significantly increased(P＜0.01).Liver swelling,inflammatory cell infiltration,and collagen deposition were significantly reduced in each treatment group compared with those in the model group,and the degree of fibrosis was reduced.Serum ALT,AST,HA,LN,PCⅢ,and COL4 were significantly decreased and ALB was significantly increased,while liver levels of HIF-1α,Notch1,Jagged1,and α-SMA proteins were also significantly decreased to varying degrees(P＜0.05).In the in vitro experiments,hypoxia promoted HSC-T6 migration and reduced apoptosis,increased the protein expression levels of HIF-1α,Notch1,Jagged1,α-SMA,and TIMP-1,and reduced the expression levels of MMP9(P＜0.01).Serum containing Jiawei Jisheng Shenqi Decoction inhibited HSC-T6 migration,promoted HSC-T6 apoptosis,lowered the expression of HIF-1α,Notch1,Jagged1,α-SMA,and TIMP-1 proteins,and enhanced the expression of MMP9 protein(P＜0.01).The inhibitory effect of Jiawei Jisheng Shenqi on HSC-T6 cell activation was reversed by the HIF-1α agonist dimethyloxalylglycine.Conclusions Jiawei Jisheng Shenqi Decoction can improve the hypoxic microenvironment via the HIF-1α/Notch pathway,thereby exerting an anti-liver cirrhosis effect.

Objective:To compare the clinical efficacy of TINAVI orthopaedic robot-assisted pedicle screw placement and free-hand pedicle screw placement in the treatment of lumbar spondylolysis in adolescents.Methods:The clinical data of 65 adolescents with lumbar spondylolysis who underwent surgery in Honghui Hospital, Xi′an Jiaotong University from January 2021 to December 2022 were analyzed retrospectively, including 20 males and 45 females with an age of (21.5 ± 4.3) years. The distribution of spondylolysis included 2 cases of L 3, 13 cases of L 4, 50 cases of L 5. According to the Meyerding classification of spondylolisthesis degree, there were 52 cases of grade Ⅰ, 5 cases of grade Ⅱ and 8 cases without spondylolisthesis, all of which were complicated with intractable back pain. All patients were treated with double segmental pedicle screw reduction and autogenous iliac bone graft. According to different screw placement methods, they were divided into TINAVI orthopedic robot-assisted screw placement group (robot group, 32 cases) and free-hand screw placement group (free-hand group, 33 cases). CT was re-examined after operation. The satisfactory rate of pedicle screw placement and cortical penetration rate were calculated according to Neo standard, and the superior articular process invasion rate of screw was calculated by Babu standard. The operation time, intra-operative blood loss, post-operative drainage, hospital stay, satisfactory rate of screw placement, cortical puncture rate and superior articular process invasion rate were compared between the two groups, and the operative complications and bony fusion time of isthmus were recorded. The visual analogue score (VAS) of lumbar pain, the score of Japanese Orthopaedic Association (JOA) and the score of Oswestry dysfunction (ODI) were compared between the two groups before operation, 1 month after operation and 1 year after operation. Results:There was no significant difference in preoperative general data between the two groups ( P>0.05). All patients completed the operation successfully, anatomical reduction was achieved in patients with spondylolisthesis. No serious operative complications such as nerve and vascular injury occurred during surgery. The operation time in the robot group was longer than that in the free-hand group: (82.6 ± 6.8) min vs. (60.5 ± 7.1) min. There was no significant difference in intra-operative blood loss, post-operative drainage and hospital stay between the two groups ( P>0.05). A total of 128 screws were placed in the robot group, and 132 screws were placed in the freehand group. There were significant differences in the satisfaction rate of screw insertion, cortical penetration rate and articular process invasion rate between the two groups: 96.9%(124/128) vs. 90.9%(120/132), 3.1%(4/128) vs. 9.1%(12/132), 2.3%(3/128) vs. 7.6%(10/132) ( P<0.05). One year after surgery, the isthmus of all patients fused well, the reduction was not lost, the intervertebral disc had no degeneration, and the instrumentation was removed. The VAS, JOA score and ODI score of the two groups at 1 month and 1 year after operation were significantly better than those before operation ( P<0.05). The VAS of the robot group was lower than that of the free-hand group at 1 month and 1 year after operation: (1.6 ± 0.8) points vs. (2.7 ± 0.9) points, (0.3 ± 0.1) points vs. (1.5 ± 0.2) points, the difference is statistically significant ( P<0.05). However, there was no significant difference in JOA score and ODI score between the two groups ( P>0.05). Conclusions:TINAVI orthopaedic robot assisted screw placement and free-hand screw placement can both effectively treat lumbar spondylolysis in adolescents. Compared with free-hand screw placement, TINAVI orthopedic robot assisted screw placement can further improve the accuracy and improve patients′ lumbodorsal pain.

Objective:To compare the clinical efficacy of TINAVI orthopaedic robot-assisted pedicle screw placement and free-hand pedicle screw placement in the treatment of lumbar spondylolysis in adolescents.Methods:The clinical data of 65 adolescents with lumbar spondylolysis who underwent surgery in Honghui Hospital, Xi′an Jiaotong University from January 2021 to December 2022 were analyzed retrospectively, including 20 males and 45 females with an age of (21.5 ± 4.3) years. The distribution of spondylolysis included 2 cases of L 3, 13 cases of L 4, 50 cases of L 5. According to the Meyerding classification of spondylolisthesis degree, there were 52 cases of grade Ⅰ, 5 cases of grade Ⅱ and 8 cases without spondylolisthesis, all of which were complicated with intractable back pain. All patients were treated with double segmental pedicle screw reduction and autogenous iliac bone graft. According to different screw placement methods, they were divided into TINAVI orthopedic robot-assisted screw placement group (robot group, 32 cases) and free-hand screw placement group (free-hand group, 33 cases). CT was re-examined after operation. The satisfactory rate of pedicle screw placement and cortical penetration rate were calculated according to Neo standard, and the superior articular process invasion rate of screw was calculated by Babu standard. The operation time, intra-operative blood loss, post-operative drainage, hospital stay, satisfactory rate of screw placement, cortical puncture rate and superior articular process invasion rate were compared between the two groups, and the operative complications and bony fusion time of isthmus were recorded. The visual analogue score (VAS) of lumbar pain, the score of Japanese Orthopaedic Association (JOA) and the score of Oswestry dysfunction (ODI) were compared between the two groups before operation, 1 month after operation and 1 year after operation. Results:There was no significant difference in preoperative general data between the two groups ( P>0.05). All patients completed the operation successfully, anatomical reduction was achieved in patients with spondylolisthesis. No serious operative complications such as nerve and vascular injury occurred during surgery. The operation time in the robot group was longer than that in the free-hand group: (82.6 ± 6.8) min vs. (60.5 ± 7.1) min. There was no significant difference in intra-operative blood loss, post-operative drainage and hospital stay between the two groups ( P>0.05). A total of 128 screws were placed in the robot group, and 132 screws were placed in the freehand group. There were significant differences in the satisfaction rate of screw insertion, cortical penetration rate and articular process invasion rate between the two groups: 96.9%(124/128) vs. 90.9%(120/132), 3.1%(4/128) vs. 9.1%(12/132), 2.3%(3/128) vs. 7.6%(10/132) ( P<0.05). One year after surgery, the isthmus of all patients fused well, the reduction was not lost, the intervertebral disc had no degeneration, and the instrumentation was removed. The VAS, JOA score and ODI score of the two groups at 1 month and 1 year after operation were significantly better than those before operation ( P<0.05). The VAS of the robot group was lower than that of the free-hand group at 1 month and 1 year after operation: (1.6 ± 0.8) points vs. (2.7 ± 0.9) points, (0.3 ± 0.1) points vs. (1.5 ± 0.2) points, the difference is statistically significant ( P<0.05). However, there was no significant difference in JOA score and ODI score between the two groups ( P>0.05). Conclusions:TINAVI orthopaedic robot assisted screw placement and free-hand screw placement can both effectively treat lumbar spondylolysis in adolescents. Compared with free-hand screw placement, TINAVI orthopedic robot assisted screw placement can further improve the accuracy and improve patients′ lumbodorsal pain.

Objective To explore the mechanism of Jiawei Jisheng Shenqi Decoction in improving the hypoxic microenvironment and antagonizing liver cirrhosis.Methods In vivo experiments were conducted using a rat model of carbon tetrachloride(CCL4)-induced liver cirrhosis.Rats were divided into normal,model,colchicine,JWJSSQ low-dose,JWJSSQ medium-dose,and JWJSSQ high-dose group.Pathological changes in liver tissues in each group were examined by hematoxylin and eosin(HE)and Masson staining,changes in serum liver function were detected using test kits,levels of hyaluronic acid(HA),laminin(LN),procollagen Ⅲ(PC Ⅲ),and collagen typeⅣ(COL4)were detected by enzyme-linked immunosorbent assay(ELISA),and protein expression levels of hypoxia-inducible factor-1α(HIF-1α),Notch1,Jagged1,and α-smooth muscle actin(α-SMA)were detected by Western blot.In vitro experiments were conducted in HSC-T6 cells,and the optimal concentration of CoCl2(100 μ mol/L,200μmol/L,400 μmol/L,600 μmol/L and 800 μmol/L)in the cultured cells and the optimal concentration of drug-containing serum(5％,10％,15％,20％)were determined by Cell Counting Kit-8(CCK-8)assay.The migration ability of cells in each group was detected by scratch testing,and changes in the apoptosis rates were determined by flow cytometry.Protein expression levels of HIF-1α,Notch1,Jagged1,α-SMA,matrix metallopeptidase 9(MMP9),and tissue inhibitor of metalloproteinases 1(TIMP-1)were detected by Western blot.Results In the in vivo experiments,liver swelling,inflammatory cell infiltration,collagen deposition,and the appearance of pseudolobules were significantly increased in the model group compared with those in the normal group.Serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),HA,LN,PCⅢ,and COL4 were significantly increased and albumin(ALB)was significantly decreased in the model group,while liver levels of HIF-1α,Notch1,Jagged1,and α-SMA proteins were significantly increased(P＜0.01).Liver swelling,inflammatory cell infiltration,and collagen deposition were significantly reduced in each treatment group compared with those in the model group,and the degree of fibrosis was reduced.Serum ALT,AST,HA,LN,PCⅢ,and COL4 were significantly decreased and ALB was significantly increased,while liver levels of HIF-1α,Notch1,Jagged1,and α-SMA proteins were also significantly decreased to varying degrees(P＜0.05).In the in vitro experiments,hypoxia promoted HSC-T6 migration and reduced apoptosis,increased the protein expression levels of HIF-1α,Notch1,Jagged1,α-SMA,and TIMP-1,and reduced the expression levels of MMP9(P＜0.01).Serum containing Jiawei Jisheng Shenqi Decoction inhibited HSC-T6 migration,promoted HSC-T6 apoptosis,lowered the expression of HIF-1α,Notch1,Jagged1,α-SMA,and TIMP-1 proteins,and enhanced the expression of MMP9 protein(P＜0.01).The inhibitory effect of Jiawei Jisheng Shenqi on HSC-T6 cell activation was reversed by the HIF-1α agonist dimethyloxalylglycine.Conclusions Jiawei Jisheng Shenqi Decoction can improve the hypoxic microenvironment via the HIF-1α/Notch pathway,thereby exerting an anti-liver cirrhosis effect.

Cerebral amyloid angiopathy (CAA) has been proven to be the most common pathological change in cerebral small vessel disease except arteriosclerosis. In recent years, with the discovery of imaging technology and new imaging markers, the diagnostic rate of CAA has greatly improved. CAA plays an important role in non-hypertensive cerebral hemorrhage and cognitive decline. This review comprehensively describes the etiology, epidemiology, pathophysiological mechanisms, clinical features, imaging manifestations, imaging markers, diagnostic criteria, and treatment of CAA to facilitate its diagnosis and treatment and reduce mortality.

Objective To explore the action mechanism of tauroursodeoxycholic acid(TUDCA)promoting intracellular clearance of Burkholderia pseudomallei(B.pseudomallei)in RAW264.7 macrophages.Methods After TUDCA of different concentrations were used to treat RAW264.7 cells pre-infected with B.pseudomallei for 8 h or not,flow cytometry was applied to detect the apoptosis of the infected and control cells.In addition,another endoplasmic reticulum stress(ERS)inhibitor 4-PBA was used to detect the apoptosis and proliferation of host cells after B.pseudomallei infection with Annexin-V/PI double staining and MTT cell proliferation assay.Furthermore,after transfected with CHOP siRNA,Western blotting and flow cytometry were employed to detect the effect of TUDCA on the expression levels of Caspase-3 and Caspase-12 and the changes in apoptotic rate after B.pseudomallei infection,respectively.Finally,the effect of TUDCA on intracellular multiplication of infected RAW264.7 cells were observed to estimate the CFU value in the presence and absence of CHOP siRNA.Results Under different concentrations of TUDCA,100 or 200 μmol/L TUDCA significantly reduced B.pseudomallei-induced apoptosis in RAW264.7 cells(P＜0.05).Meanwhile,both TUDCA and 4-PBA treatment could decrease the apoptosis induced by B.pseudomallei infection by ERS(P＜0.05).Further,the expression levels of Caspase-3 and Caspase-12 were obviously increased after B.pseudomallei infection compared with uninfected groups,but their expression levels in the siCHOP group was significantly lower than that in the siC group.Besides,flow cytometry also showed that TUDCA could reduce apoptosis induced by B.pseudomallei infection(P＜0.05),but no significant effect of TUDCA on apoptosis was observed under CHOP knockdown.Finally,intracellular CFU assay indicated that TUDCA treatment promoted the host cell clearance of B.pseudomallei(P＜0.05),but no such effect was observed in siCHOP group.Conclusion In B.pseudomallei infected RAW264.7 cells,TUDCA promotes the intracellular clearance of the bacteria by inhibiting ERS-induced apoptosis.

The development,progression,and curative efficacy of head and neck squamous cell carcinoma(HNSCC)are influenced by complex interactions between epithelial and immune cells.Nevertheless,the specific changes in the nature of these interactions and their underlying molecular mechanisms in HNSCC are not yet fully understood.Cuproptosis,a form of programmed cell death that is dependent on copper,has been implicated in cancer pathogenesis.However,the understanding of cuproptosis in the context of HNSCC remains limited.In this study,we have discovered that cuproptosis-related long non-coding RNAs(CRLs)known as JPX play a role in promoting the expression of the oncogene urokinase-type plasminogen activator(PLAU)by competitively binding to miR-193b-3p in HNSCC.The increased activity of the JPX/miR-193b-3p/PLAU axis in malignant epithelial cells leads to enhanced cell proliferation,migration,and invasion in HNSCC.Moreover,the overexpression of PLAU in tumor epithelial cells facilitates its interaction with the receptor PLAUR,predominantly expressed on macrophages,thereby influencing the abnormal epithelial-immune interactome in HNSCC.Notably,the JPX inhibitor Axitinib and the PLAU inhibitor Palbociclib may not only exert their effects on the JPX/miR-193b-3p/PLAU axis that impacts the malignant tumor behaviors and the epithelial-immune cell interactions but also exhibit synergistic effects in terms of suppressing tumor cell growth and arresting cell cycle by targeting epidermal growth factor receptor(EGFR)and cyclin-dependent kinase(CDK4/6)for the treatment of HNSCC.

The development, progression, and curative efficacy of head and neck squamous cell carcinoma (HNSCC) are influenced by complex interactions between epithelial and immune cells. Nevertheless, the specific changes in the nature of these interactions and their underlying molecular mechanisms in HNSCC are not yet fully understood. Cuproptosis, a form of programmed cell death that is dependent on copper, has been implicated in cancer pathogenesis. However, the understanding of cuproptosis in the context of HNSCC remains limited. In this study, we have discovered that cuproptosis-related long non-coding RNAs (CRLs) known as JPX play a role in promoting the expression of the oncogene urokinase-type plasminogen activator (PLAU) by competitively binding to miR-193b-3p in HNSCC. The increased activity of the JPX/miR-193b-3p/PLAU axis in malignant epithelial cells leads to enhanced cell proliferation, migration, and invasion in HNSCC. Moreover, the overexpression of PLAU in tumor epithelial cells facilitates its interaction with the receptor PLAUR, predominantly expressed on macrophages, thereby influencing the abnormal epithelial-immune interactome in HNSCC. Notably, the JPX inhibitor Axitinib and the PLAU inhibitor Palbociclib may not only exert their effects on the JPX/miR-193b-3p/PLAU axis that impacts the malignant tumor behaviors and the epithelial-immune cell interactions but also exhibit synergistic effects in terms of suppressing tumor cell growth and arresting cell cycle by targeting epidermal growth factor receptor (EGFR) and cyclin-dependent kinase (CDK4/6) for the treatment of HNSCC.
Humans ; MicroRNAs/metabolism* ; RNA, Long Noncoding/metabolism* ; Head and Neck Neoplasms/metabolism* ; Cell Proliferation ; Squamous Cell Carcinoma of Head and Neck/genetics* ; Urokinase-Type Plasminogen Activator/genetics* ; Cell Movement ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Carcinoma, Squamous Cell/genetics* ; Neoplasm Invasiveness

Objective:To investigate the mechanism of Wenjing Decoction in the treatment of hepatic fibrosis through network pharmacological methods, and conducting animal experiments to verify the core targets.Methods:The TCMSP database platform was used to screen the active components and related targets of Wenjing Decoction, and the Uniprot database was used to obtain the target genes corresponding to the active components of Wenjing Decoction. The network diagram of "Chinese materia medica-compound-target" was constructed in Cytoscape 3.7.2, and the GeneCards database was used to search liver fibrosis related targets. String database was used to construct a protein interaction network (PPI) to screen the core components and key targets of liver fibrosis, and GO analysis and KEGG pathway enrichment were performed. Animal experiments were conducted to verify the results of the analysis. 10 mice were selected as the blank group, and the remaining 45 rats were induced with carbon tetrachloride induced liver fibrosis model. After modeling, 40 successfully modeled rats were divided into model group and Wenjing Decoction high, medium-, and low-dosage groups using a random number table method, with 10 rats in each group. Wenjing Decoction high, medium-, and low-dosage groups were orally administered with 1.5×3.18, 3.18, and 0.5×3.18 g/kg Wenjing Decoction, respectively. The blank group was orally administered with equal volume distilled water once a day for 8 consecutive weeks. HE staining was used to observe the histopathological and morphological changes in the liver of rats. The serum GPT and GOT levels of rats were detected using a fully automated biochemical analyzer, and the expressions of TNF, AKT, and IL-6 proteins in rat liver tissue was detected using Western Blot.Results:A total of 188 active components of Wenjing Decoction were obtained, and the active components with higher degree values were β-sitosterol, quercetin, naringenin, etc. 799 liver fibrosis gene targets were collected, and the core target genes of the PPI network were TNF, AKT, IL6, etc. The key anti-hepatic fibrosis related pathways were obtained by GO function and KEGG analysis, including pathway in cancer, TNF, PI3K-Akt and other signalling pathways. Results of animal experiments showed that there were obvious inflammatory infiltration, collagen fibre and pseudo lobe generation in the liver tissue of rats in the model group, and the levels of inflammation and fibrosis in the liver tissue of rats in the Wenjing Decoction high, medium-, and low-dosage groups were improved to different degrees compared with that of the model group; compared with the model group, the levels of serum GPT and GOT decreased ( P<0.05); the protein expressions of TNF, AKT and IL6 in the Wenjing Decoction high, medium-, and low-dosage groups decreased ( P<0.05). Conclusion:Wenjing Decoction may exert anti-liver fibrosis effects by intervening in TNF, AKT, IL6 targets, regulating cancer pathways, TNF, PI3K Akt and other signaling pathways.