AIM:This study aimed to utilize network pharmacology and an anxiety rat model to investigate the intervention targets and underlying mechanisms of Baixiangdan capsule(BXD)in the treatment of anxiety-like behavior.METHODS:We screened the action targets of BXD on the anxiety model using network pharmacology,followed by Gene Ontology(GO)enrichment and the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis of the identified targets.Additionally,we evaluated the effects of BXD on rat anxiety behaviors induced by foot shock,with measurement of serum level of c-Jun N-terminal kinase inhibitor(JIK),and the protein levels of c-Jun N-terminal kinase(JNK),phos-phorylated JNK(p-JNK)and JIK in the left hippocampus and hypothalamus.RESULTS:A total of 97 targets,including the dopamine D1/D3 receptors,were identified as intersection targets.GO enrichment analysis indicated that target pro-teins were significantly involved in molecular functions such as catecholamine binding,receptor activation,and signal transduction.KEGG pathway analysis revealed that neural receptor-ligand pathways,including dopaminergic synapses(15%)and neuroactive ligand-receptor interaction(18%),were notably represented.In behavioral experiments,BXD and diazepam treatments significantly reduced total path in the open-field test(P＜0.01),while the number of entries into the central region increased(P＜0.05).Additionally,the percentage of entry times of the open arm and the percentage of time spent in the open arm were also increased(P＜0.01).Furthermore,BXD treatment led to decreased ratio of p-JNK/JNK and increased level of JIK(P＜0.05).CONCLUSION:The traditional Chinese medicine BXD demonstrates a promising efficacy in alleviating anxiety-like behaviors in model rats.It operates through a multi-component,multi-target,and multi-pathway approach,primarily by modulating the JIK/JNK signaling pathway.

Objective:To explore the value of four-dimensional flow (4D Flow) MRI in evaluating hemodynamic changes of transplant renal artery stenosis (TRAS).Methods:The study was a cross-sectional study. A retrospective analysis of 67 patients after renal transplantation was performed in Third Affiliated Hospital of Soochow University from January 2021 to October 2022. All patients were examined with non-contrast enhanced magnetic resonance angiography (NCE-MRA) and 4D Flow MRI. After NCE-MRA assessment, the patients were divided into a non stenosis group (39 cases), non-obvious stenosis group (stenosis degree<50%, 13 cases) and obvious stenosis group (stenosis degree≥50%, 15 cases). The 4D Flow MRI data were analyzed using the post-processing software CVI42 (Canada) to measure hemodynamic parameters of the transplanted renal artery in the non-stenosis group, as well as the proximal, central, and distal regions of the stenosis in the non-obvious stenosis group and obvious stenosis group. The parameters included net flow rate, maximum flow rate, average velocity, peak velocity, average wall shear stress, and maximum wall shear stress. One way analysis of variance and least significant difference (LSD) were used to test the differences of hemodynamic parameters among the three groups and between the proximal, central and distal regions of the stenosis. Pearson correlation coefficient was used to evaluate the correlation between hemodynamic parameters of transplant renal artery and estimated glomerular filtration rate (eGFR).Results:The net flow, maximum flow and average velocity at the proximal region of stenosis in the group with obvious stenosis of transplanted renal artery were significantly lower than those in the non-stenosis group and the non-obvious stenosis group (all P<0.05). The net flow and maximum flow at the distal region of stenosis in both obvious stenosis group and non-obvious stenosis group were lower than those in non-stenosis group, and the differences were statistically significant (both P<0.001). The mean velocity and peak velocity at the distal region of stenosis in the obvious stenosis group were higher than those in the non-stenosis group, and the differences were statistically significant (both P<0.05). The maximum and average wall shear stress at the distal region of stenosis in the obvious stenosis group were lower than those in the non-stenosis group and the non-obvious stenosis group, and the differences were statistically significant (both P<0.05). The net flow and maximum flow in the center region of stenosis were lower than those in the proximal region of stenosis, and the differences were statistically significant (both P<0.05). The peak velocity in the center region and distal region of stenosis was higher than those in the proximal region of stenosis, and the difference was statistically significant (both P<0.05). There was a positive correlation between the net flow and eGFR at the TRAS patients proximal, center, and distal stenosis ( r=0.270, 0.260, 0.320, respectively, P=0.044, 0.041, 0.036, respectively). There was a positive correlation between the maximum flow and eGFR at the TRAS patients proximal, center, and distal stenosis ( r=0.306, 0.276, 0.269, respectively, P=0.037, 0.041, 0.043, respectively). Conclusion:After TRAS, there is a significant change in blood flow status. The 4D Flow MRI can provide quantitative hemodynamic parameters to reflect the hemodynamic changes of TRAS.

Objective:To observe the expression of T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain(TIGIT)in tumor tissue and peripheral blood CD8+T cells in patients with triple-negative breast cancer(TNBC),and to explore the ef-fect of tiragolumab on the function of CD8+T cells in the peripheral blood of these patients.Methods:The expression of TIGIT in tumor tissue of patients with TNBC was analyzed using The Cancer Genome Atlas(TCGA)database and immunohistochemical staining.Flow cytometry was employed to assess the co-expression of TIGIT and programmed death-1(PD-1)in peripheral blood CD8+T cells,as well as their cytokine secretion.A co-culture model of CD8+T cells and TNBC cell lines,HCC-1937 and MDA-MB-231,was estab-lished.The effect of tiragolumab on the anti-tumor activity of CD8+T cells in patients with TNBC was investigated using flow cytometry and confocal fluorescence imaging.Results:The expression of TIGIT in tumor tissue and peripheral blood CD8+T cells of patients with TNBC was significantly increased(P<0.05).Compared with the healthy control group,the TNBC group showed a significantly larger number of TIGIT+PD-1+CD8+T cells in the peripheral blood and significantly reduced secretion of interferon gamma(IFN-γ),tumor necrosis factor-α(TNF-α),and ginkgolide B(GB)by CD8+T cells;specifically,TIGIT+CD8+T cells demonstrated significantly re-duced secretion compared with TIGIT-CD8+T cells(P<0.05).Fol-lowing treatment with tiragolumab,TIGIT+CD8+T cells exhibited increased secretion of IFN-γ and TNF-α(P<0.05).In the co-culture model,tiragolumab restored the apoptosis-inducing ability of CD8+T cells in patients with TNBC,and this ability was further enhanced when it was combined with envafolimab.Conclusion:Ti-ragolumab restores the tumor-killing function of CD8+T cells by im-proving their immunosuppression.The combination of tiragolumab with envafolimab can further enhance its anti-tumor effect.

Objective The aim of this study was to investigate the expression of nuclear pore membrane protein 121(POM121)in head and neck mucosal melanoma(HNMM)and its effect on the migration and invasion of HNMM cells.Methods The cancer tissues from 63 patients with HNMM and 20 adjacent normal oral epithelial tissues who were treated in the Harbin Cancer Hos-pital of Harbin Medical University from March 1,2011 to March 30,2015 were collected,and the expression of POM121 was detected by immunohistochemistry.The relationship between the expression of POM121 and the clinicopathological features of HNMM patients and its effect on the prognosis of patients were analyzed.Western blot was used to detect the expression of POM121 in HNMM cells(MM9H-1 cells)and human oral epithelial cells(human oral keratinocytes,HOK cells).After knocking down POM121 with small in-terfering RNA(siRNA),the effects on the migration and invasion of HNMM cells were detected by Scratch assay and Transwell assay.Results Immunohistochemistry showed that expression of POM121 was significantly higher in HNMM tissues than that in adjacent tissues(P<0.001).The expression of POM121 was associated with tumor size and stage(P<0.05).Kaplan-Meier analysis showed that the disease-free survival(DFS)and overall survival(OS)of patients with low expression of POM121 were significantly longer than those with high expression of POM121.Cox regression analysis showed that POM121 expression,AJCC stage and lymph node metasta-sis were influencing factors for OS and DFS of HNMM patients(P<0.05).Western blot results showed that the expression of POM121 protein in MM9H-1 cells was significantly higher than that in HOK cells(P<0.05).After knocking down POM121,the cell migration rate and cell invasion ability were significantly reduced(P<0.001).Conclusion POM121 is highly expressed in HNMM tissues and cells,and down-regulation of POM121 significantly inhibits the migration and invasion of HNMM cells.

AIM:This study aimed to utilize network pharmacology and an anxiety rat model to investigate the intervention targets and underlying mechanisms of Baixiangdan capsule(BXD)in the treatment of anxiety-like behavior.METHODS:We screened the action targets of BXD on the anxiety model using network pharmacology,followed by Gene Ontology(GO)enrichment and the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis of the identified targets.Additionally,we evaluated the effects of BXD on rat anxiety behaviors induced by foot shock,with measurement of serum level of c-Jun N-terminal kinase inhibitor(JIK),and the protein levels of c-Jun N-terminal kinase(JNK),phos-phorylated JNK(p-JNK)and JIK in the left hippocampus and hypothalamus.RESULTS:A total of 97 targets,including the dopamine D1/D3 receptors,were identified as intersection targets.GO enrichment analysis indicated that target pro-teins were significantly involved in molecular functions such as catecholamine binding,receptor activation,and signal transduction.KEGG pathway analysis revealed that neural receptor-ligand pathways,including dopaminergic synapses(15%)and neuroactive ligand-receptor interaction(18%),were notably represented.In behavioral experiments,BXD and diazepam treatments significantly reduced total path in the open-field test(P＜0.01),while the number of entries into the central region increased(P＜0.05).Additionally,the percentage of entry times of the open arm and the percentage of time spent in the open arm were also increased(P＜0.01).Furthermore,BXD treatment led to decreased ratio of p-JNK/JNK and increased level of JIK(P＜0.05).CONCLUSION:The traditional Chinese medicine BXD demonstrates a promising efficacy in alleviating anxiety-like behaviors in model rats.It operates through a multi-component,multi-target,and multi-pathway approach,primarily by modulating the JIK/JNK signaling pathway.

Objective The aim of this study was to investigate the expression of nuclear pore membrane protein 121(POM121)in head and neck mucosal melanoma(HNMM)and its effect on the migration and invasion of HNMM cells.Methods The cancer tissues from 63 patients with HNMM and 20 adjacent normal oral epithelial tissues who were treated in the Harbin Cancer Hos-pital of Harbin Medical University from March 1,2011 to March 30,2015 were collected,and the expression of POM121 was detected by immunohistochemistry.The relationship between the expression of POM121 and the clinicopathological features of HNMM patients and its effect on the prognosis of patients were analyzed.Western blot was used to detect the expression of POM121 in HNMM cells(MM9H-1 cells)and human oral epithelial cells(human oral keratinocytes,HOK cells).After knocking down POM121 with small in-terfering RNA(siRNA),the effects on the migration and invasion of HNMM cells were detected by Scratch assay and Transwell assay.Results Immunohistochemistry showed that expression of POM121 was significantly higher in HNMM tissues than that in adjacent tissues(P<0.001).The expression of POM121 was associated with tumor size and stage(P<0.05).Kaplan-Meier analysis showed that the disease-free survival(DFS)and overall survival(OS)of patients with low expression of POM121 were significantly longer than those with high expression of POM121.Cox regression analysis showed that POM121 expression,AJCC stage and lymph node metasta-sis were influencing factors for OS and DFS of HNMM patients(P<0.05).Western blot results showed that the expression of POM121 protein in MM9H-1 cells was significantly higher than that in HOK cells(P<0.05).After knocking down POM121,the cell migration rate and cell invasion ability were significantly reduced(P<0.001).Conclusion POM121 is highly expressed in HNMM tissues and cells,and down-regulation of POM121 significantly inhibits the migration and invasion of HNMM cells.

Objective:To explore the value of four-dimensional flow (4D Flow) MRI in evaluating hemodynamic changes of transplant renal artery stenosis (TRAS).Methods:The study was a cross-sectional study. A retrospective analysis of 67 patients after renal transplantation was performed in Third Affiliated Hospital of Soochow University from January 2021 to October 2022. All patients were examined with non-contrast enhanced magnetic resonance angiography (NCE-MRA) and 4D Flow MRI. After NCE-MRA assessment, the patients were divided into a non stenosis group (39 cases), non-obvious stenosis group (stenosis degree<50%, 13 cases) and obvious stenosis group (stenosis degree≥50%, 15 cases). The 4D Flow MRI data were analyzed using the post-processing software CVI42 (Canada) to measure hemodynamic parameters of the transplanted renal artery in the non-stenosis group, as well as the proximal, central, and distal regions of the stenosis in the non-obvious stenosis group and obvious stenosis group. The parameters included net flow rate, maximum flow rate, average velocity, peak velocity, average wall shear stress, and maximum wall shear stress. One way analysis of variance and least significant difference (LSD) were used to test the differences of hemodynamic parameters among the three groups and between the proximal, central and distal regions of the stenosis. Pearson correlation coefficient was used to evaluate the correlation between hemodynamic parameters of transplant renal artery and estimated glomerular filtration rate (eGFR).Results:The net flow, maximum flow and average velocity at the proximal region of stenosis in the group with obvious stenosis of transplanted renal artery were significantly lower than those in the non-stenosis group and the non-obvious stenosis group (all P<0.05). The net flow and maximum flow at the distal region of stenosis in both obvious stenosis group and non-obvious stenosis group were lower than those in non-stenosis group, and the differences were statistically significant (both P<0.001). The mean velocity and peak velocity at the distal region of stenosis in the obvious stenosis group were higher than those in the non-stenosis group, and the differences were statistically significant (both P<0.05). The maximum and average wall shear stress at the distal region of stenosis in the obvious stenosis group were lower than those in the non-stenosis group and the non-obvious stenosis group, and the differences were statistically significant (both P<0.05). The net flow and maximum flow in the center region of stenosis were lower than those in the proximal region of stenosis, and the differences were statistically significant (both P<0.05). The peak velocity in the center region and distal region of stenosis was higher than those in the proximal region of stenosis, and the difference was statistically significant (both P<0.05). There was a positive correlation between the net flow and eGFR at the TRAS patients proximal, center, and distal stenosis ( r=0.270, 0.260, 0.320, respectively, P=0.044, 0.041, 0.036, respectively). There was a positive correlation between the maximum flow and eGFR at the TRAS patients proximal, center, and distal stenosis ( r=0.306, 0.276, 0.269, respectively, P=0.037, 0.041, 0.043, respectively). Conclusion:After TRAS, there is a significant change in blood flow status. The 4D Flow MRI can provide quantitative hemodynamic parameters to reflect the hemodynamic changes of TRAS.

Objective:To study the clinically curative effect of ureteroscopic holmium laser lithotripsy combined with intercepted basket of capture and extraction device for stone(N-trap)in treating middle and upper ureteral stones.Methods:A total of 112 patients with middle and upper ureteral stone who were diagnosed and treated in the Department of Urology of the Second Affiliated Hospital of Wannan Medical College from September 2020 to September 2022 were prospectively selected as the study subjects,and they were divided into two groups according to the random number table method,with 56 cases in each group.The control group was treated with ureteroscopic holmium laser lithotripsy alone,and the observation group was treated with ureteroscopic holmium laser lithotripsy combined with N-trap intercepted basket for treatment.The related indicators of surgery,the stone removal effect,renal function indicators,postoperative renal mass,postoperative recurrence and postoperative complications between two groups were compared.The scores of the Wisconsin Stone Quality of Life(WISQOL)questionnaire were used to compare and evaluate the postoperative quality of life between the two groups.Results:There were no significant differences in intraoperative operation time and intraoperative blood loss between the two groups(P>0.05),and the postoperative hospitalization time in the observation group was significantly shorter than that in the control group(t=3.464,P<0.05).The success rate of one-time lithotripsy and the clearance rate of stone within 30 d in the observation group were significantly higher than those in the control group,and the upward movement rate of stones of the observation group was significantly lower than that in the control group,and the difference was statistically significant(x2=6.698,7.240,5.489,P<0.05),respectively.The postoperative serum creatinine(Scr),blood urea nitrogen(BUN)and urine microalbumin(UMA)in the observation group were significantly lower than those in the control group,and the differences were statistically significant(t=6.320,8.115,9.231,P<0.05),respectively.The degree of hydronephrosis at 3,6 and 12 months after surgery in the observation group were significantly lower than those in the control group,and the differences were statistically significant(t=3.218,3.345,2.985,P<0.05),respectively.The recurrence rates at 6 and 12 months after surgery in the inspection group were significantly lower than those in the control group,and the differences were statistically significant(x2=5.114,5.783,P<0.05),respectively.The incidence of postoperative complication in the observation group was significantly lower than that in the control group(x2=4.865,P<0.05).The total score of the each dimension of WISQOL scale,and the total score of energy,sleep status,physical symptoms and overall emotion in the observation group were significantly higher than those in the control group,and the differences were statistically significant(t=3.734,3.889,3.903,4.340,4.650,P<0.05),respectively.Conclusion:The curative effect of ureteroscopic holmium laser lithotripsy combined with N-trap intercepted basket is certain,which can effectively improve the clearance rate of stone,and shorten the postoperative hospitalization time,and reduce the incidence of postoperative complications and recurrence rate,and promote the recovery of renal function,and improve the quality of life of patients after surgery.

Objective To evaluate the safety and efficacy of 450 nm blue laser vaporization prostatectomy in the treatment of benign prostatic hyperplasia(BPH).Methods A retrospective analysis was conducted on 40 BPH patients treated with 450 nm blue laser vaporization prostatectomy at our hospital during Mar.and Nov.2023.The preoperative and postoperative maximum urinary flow rate(Qmax),post-void residual volume(PVR),international prostate symptom score(IPSS),and quality of life(QoL)score were compared.The operation time,postoperative bladder irrigation time,and postoperative hemoglobin decrease were recorded.Results All operations were successful.One month after surgery,the Qmax[(7.9±2.1)mL/s vs.(16.8±2.5)mL/s]was significantly higher,while PVR[(110.0±42.1)mL vs.(14.6±11.4)mL],IPSS[(25.0±3.1)vs.(11.8±4.0)],and QoL[(5.1±0.9)vs.(2.5±0.6)]were significantly lower,with statistical significance(P＜0.05).The operation time was(52.5±15.5)min,the bladder irrigation time was(22.3±4.9)h,the postoperative hemoglobin drop was(6.5±3.8)g/L.Urinary retention occurred in 2 patients after removal of the catheter.Gross hematuria occurred in 1 patient after discharge.Conclusion Vaporization prostatectomy with 450 nm blue laser can significantly improve clinical symptoms and perioperative safety,with high vaporization efficiency and good hemostatic effects.It is worthy of clinical promotion and application.

BACKGROUND:Tissue engineering has brought new hope to the clinical challenge of liver failure,and the preparation of plant-derived decellularized fiber scaffolds holds significant importance in liver tissue engineering. OBJECTIVE:To prepare apple tissue decellularized scaffold material by using fresh apple slices and a solution of sodium dodecyl sulfate,and assess its biocompatibility. METHODS:Fresh apples were subjected to decellularization using phosphate buffer saline and sodium dodecyl sulfate solution,separately.Afterwards,the decellularized apple tissues and apple decellularized scaffold materials were decontaminated with phosphate buffer saline.Subsequently,scanning electron microscopy was used to assess the effectiveness of decellularization of the apple materials.Adipose-derived mesenchymal stem cells were extracted from the inguinal fat BALB/C of mice,and their expression of stem cell-related markers(CD45,CD34,CD73,CD90,and CD105)was identified through flow cytometry.The cells were then divided into a scaffold-free control group and a scaffold group.Equal amounts of adipose-derived mesenchymal stem cells were seeded onto both groups.The biocompatibility of the decellularized scaffold with adipose-derived mesenchymal stem cells was evaluated using CCK-8 assay,hematoxylin-eosin staining,and phalloidine staining.Cell adhesion and growth on the scaffold were observed under light microscopy and scanning electron microscopy.Furthermore,the scaffold was subdivided into the non-induced group and the hepatogenic-induced group.Adipose-derived mesenchymal stem cells were cultured on the decellularized apple scaffold,and they were cultured for 14 days in regular culture medium or hepatogenic induction medium for comparison.Immunofluorescent staining using liver cell markers,including albumin,cytokeratin 18,and CYP1A1,was performed.Enzyme-linked immunosorbent assay was used to detect the secretion of alpha fetoprotein and albumin.Additionally,scanning electron microscopy was employed to observe the morphology of the induced cells on the scaffold,verifying the expression of liver cell-related genes on the decellularized scaffold material.Finally,the cobalt-60 irradiated and sterilized decellularized apple scaffolds were transplanted onto the surface of mouse liver and the degradation of the scaffold was observed by gross observation and hematoxylin-eosin staining after 28 days. RESULTS AND CONCLUSION:(1)The scanning electron microscopy results revealed that the decellularized apple scaffold material retained a porous structure of approximately 100 μm in size,with no residual cells observed.(2)Through flow cytometry analysis,the cultured cells were identified as adipose-derived mesenchymal stem cells.(3)CCK-8 assay results demonstrated that the prepared decellularized apple tissue scaffold material exhibited no cytotoxicity.Hematoxylin-eosin staining and phalloidine staining showed that adipose-derived mesenchymal stem cells were capable of adhering and proliferating on the decellularized apple tissue scaffold.(4)The results obtained from immunofluorescence staining and enzyme-linked immunosorbent assay revealed that adipose-derived mesenchymal stem cells cultured on the decellularized apple scaffolds exhibited elevated expression of liver-specific proteins,including albumin,alpha-fetoprotein,cytokeratin 18,and CYP1A1.These results suggested that they were induced differentiation into hepatocyte-like cells possessing functional characteristics of liver cells.(5)The decellularized apple scaffold implanted at 7 days has integrated with the liver,with partial degradation of the scaffold observed.By 28 days,the decellularized apple scaffold has completely degraded and has been replaced by newly-formed tissue.(6)The results indicate that the decellularized scaffold material derived from apple tissue demonstrates favorable biocompatibility,promoting the proliferation,adhesion,and hepatic differentiation of adipose-derived mesenchymal stem cells.