Objective To explore the impact of different moving patterns during the dip-coating process on thickness distributions of polymer heart valves.Methods Based on the volume of fluid(VOF)multiphase flow model,the Eulerian wall-film(EWF)model,and dynamic mesh technology,the dip-coating manufacturing process of polymer heart valves were numerically simulated.The effects of vertical,horizontal,and circular moving patterns on flow characteristics of the surface impregnation liquid and liquid film distributions under self-rotation conditions of the models were mainly studied.Subsequently,seven identical test points were set on each valve leaflet to collect thickness data,and the coefficient of variation(CV)was calculated to evaluate the uniformity of the liquid film thickness.Given that the vertical and horizontal patterns had fewer moving planes,limiting the optimization space,the circular pattern(45°)with richer moving planes was selected as the basis for optimization,and comparative analysis of numerical simulation was conducted.Results In the vertical pattern,the peak CV was 0.461 3;in the horizontal pattern,the CV was 0.060 8;and in the circular pattern,the CV at 30°,45° and 60° were 0.457 5,0.272 8,and 0.255 6,respectively.After optimization,the CV for the circular pattern(45°)decreased to 0.052 5,representing an 80.7％reduction compared to the pre-optimization value.Conclusions The moving patterns significantly affect the uniformity of dip-coating thickness distributions.The horizontal pattern demonstrates the best uniformity,while the vertical pattern shows the poorest uniformity.The CV for the circular pattern decreases as the angle increases,with its uniformity between that of the vertical and horizontal patterns.Optimization of moving pattern parameters based on simulation results has improved the uniformity of thickness distributions.

Objective:To investigate the clinical characteristics of cervical adenocarcinoma and analyze the survival status and related prognostic factors.Methods:The data of 229 patients with cervical adenocarcinoma who were diagnosed pathologically in the General Hospital of Ningxia Medical University from January 2013 to October 2022 were retrospectively analyzed. Among them, 198 early stage patients were mainly treated with surgery, and 31 locally advanced stage patients were mainly treated with chemoradiotherapy. The overall survival (OS) and progression-free survival (PFS) rates in the whole cohort of patients and different treatment subgroups were calculated. Kaplan‐Meier method and log‐rank test were used for survival analysis, and Cox proportional hazards model was used for univariate and multivariate survival analyses.Results:Among the 229 patients, there were 11 subtypes of pathological classifications, predominantly of the usual‐type. At the end of follow‐up, 57 patients (24.9%) relapsed. The 3‐ and 5‐year OS rates were 86.4% and 79.3%, respectively, and the 3‐ and 5‐year PFS rates were 81.6% and 73.6%, respectively. Multivariate analysis showed that International Federation of Gynecology and Obstetrics (FIGO) staging of stages Ⅲ‐Ⅳ was an independent prognostic factor for OS and PFS ( HR=2.033, 95% CI=1.456‐2.839, P<0.001; HR=1.701, 95% CI=1.251‐2.313, P=0.001). Lymph node metastasis was an independent risk factor for PFS ( HR=1.610,95% CI=1.021‐2.539, P=0.041). Subgroup analysis of 198 patients with surgical treatment: the 3‐ and 5‐year OS rates were 90.0% and 84.9%, and the 3‐ and 5‐year PFS rates were 82.7% and 76.7%, respectively. Multivariate analysis showed that lymph node metastasis and deep invasion depth were the main risk factors for OS ( HR=6.893, 95% CI=2.592‐18.327, P<0.001; HR=1.952, 95% CI=1.164‐3.272, P=0.011) and PFS ( HR=5.507, 95% CI=2.569‐11.805, P<0.001; HR=1.638, 95% CI=1.09‐2.461, P=0.018). Ovarian preservation was an independent risk factor for PFS ( HR=3.364, 95% CI=1.115‐10.151, P=0.031). Conclusions:The pathological types of cervical adenocarcinoma are complex and diverse. Local recurrence and distant metastasis are the main reasons for treatment failure. FIGO stage, lymph node metastasis and postoperative depth of invasion are the main prognostic factors of cervical adenocarcinoma.

Objective:To investigate the role of mechanosensor Yes-associated protein 1 (YAP1) in urothelial cells in inducing bladder dysfunction in a partial bladder outlet obstruction (pBOO) model.Methods:Ten female C57BL/6 mice were included in this study and randomly divided into pBOO and sham groups based on body weight using a stratified pairing method, with 5 mice in each group. The pBOO group underwent proximal urethral ligation surgery, while the sham group underwent a sham operation. Two weeks after surgery, the urinary pattern was analyzed using the urine spot test. The significant increase in urine spot numbers indicated the successful establishment of the pBOO model. The mice were then sacrificed, and bladder tissues were weighed and stained with hematoxylin and eosin (HE) to observe morphological changes. The bladder urothelial layer was further isolated, and total cell proteins were extracted to detect the expression levels of YAP1 protein using Western blotting. Mouse immortalized bladder urothelial cells were divided into three experimental groups: the negative control (NC) group, which was treated with YAP1-NC lentivirus; the overexpression (OE) group, which was treated with YAP1-OE lentivirus to induce YAP1 protein overexpression; and the verteporfin treatment (VP) group, which was treated with verteporfin on the basis of the OE group. Real-time quantitative PCR and Western blotting were used to verify the transcription and expression levels of YAP1 protein, the co-transcriptional activator TEAD4 protein, and the phosphorylated protein DRP1-616 (at serine 616) of dynamin-related protein 1 (DRP1). An ATP detection kit was used to measure the ATP release concentration in the NC, OE, and VP groups. The interaction between YAP1 and TEAD4 was investigated using co-immunoprecipitation, and the expression of the mitochondrial marker translocase of the outer mitochondrial membrane 20 (Tom20) was observed using immunofluorescence staining.Results:The results of the urine spot test showed that the number of urine spots on the filter paper in the pBOO group was higher than that in the sham group within 6 hours [(283.0±9.1) spots vs. (3.7±0.3) spots, P<0.01], and the urine spots were scattered. The bladder wet weight in the pBOO group was significantly higher than that in the sham group [(105.70±6.84) mg vs. (22.33±1.20) mg, P<0.01]. Histological observations revealed reduced bladder mucosal folds and increased detrusor muscle thickness in the pBOO group. The expression of YAP1 protein in the bladder urothelial cells of the pBOO group was significantly upregulated compared to the sham group [(1.26±0.08) vs. (0.50±0.04), P<0.01]. In vitro experiments showed that compared to the NC group, the OE group had significantly increased expression of DRP1-616 [(0.94±0.05) vs. (0.33±0.01), P<0.01] and higher ATP release concentration [(24.45±0.16) μmol/mg vs. (19.67±0.42) μmol/mg, P<0.01]. In contrast, the VP group had significantly decreased expression of DRP1-616 [(0.29±0.04) vs. (0.94±0.05), P<0.01] and lower ATP release concentration [(10.55±0.01) μmol/mg vs. (24.45±0.16) μmol/mg, P<0.01] compared to the OE group. Co-immunoprecipitation experiments using YAP1 and TEAD4 antibodies showed that YAP1 and TEAD4 proteins could interact and form a transcriptional complex to regulate ATP release. Immunofluorescence staining revealed increased expression of Tom20 in the OE group compared to the NC group [(104.20±3.28) vs. (74.51±3.87), P<0.01]. Conclusions:In the pBOO-induced bladder dysfunction model, YAP1 is highly expressed in urothelial cells. YAP1 forms a transcriptional complex with TEAD4 to regulate ATP release by promoting mitochondrial fission via DRP1-616 expression, which is a key mechanism underlying pBOO-induced bladder dysfunction.

BACKGROUND: The protective effect of mesenchymal stem cells (MSCs) on cardiac ischemia-reperfusion (I/R) injury has been widely reported. Dental pulp-derived mesenchymal stem cells (DP-MSCs) have therapeutic effects on various diseases, including diabetes and cirrhosis. This study aimed to determine the therapeutic effects of DP-MSCs on I/R injury and elucidate the underlying mechanism. METHODS: Myocardial I/R injury model mice were treated with DP-MSCs or a miR-19a-3p mimic. The infarct volume, fibrotic area, pyroptosis, inflammation level, and cardiac function were measured. Cardiomyocytes exposed to hypoxia-reoxygenation were transfected with the miR-19a-3p mimic, miR-19a-3p inhibitor, or negative control. Pyroptosis and protein expression in the interferon regulatory factor 8/mitogen-activated protein kinase (IRF-8/MAPK) pathway were measured. RESULTS: DP-MSCs protected cardiac function in cardiac I/R-injured mice and inhibited cardiomyocyte pyroptosis. The upregulation of miR-19a-3p protected cardiac function, inhibited cardiomyocyte pyroptosis, and inhibited IRF-8/MAPK signaling in cardiac I/R-injured mice. DP-MSCs inhibited cardiomyocyte pyroptosis and the IRF-8/MAPK signaling by upregulating the miR-19a-3p levels in cardiomyocytes injured by I/R. CONCLUSION DP-MSCs protected cardiac function by inhibiting cardiomyocyte pyroptosis through miR-19a-3p under I/R conditions.
Animals ; MicroRNAs/metabolism* ; Pyroptosis/genetics* ; Mesenchymal Stem Cells/metabolism* ; Myocytes, Cardiac/cytology* ; Mice ; Male ; Mice, Inbred C57BL ; Dental Pulp/cytology* ; Myocardial Reperfusion Injury/therapy* ; MAP Kinase Signaling System/physiology*

Objective To investigate the impact of eccentric placement for various types of artificial aortic valves on downstream flow dynamics.Methods A physiological pulsatile circulation simulation system was employed and particle image velocimetry(PIV)was utilized to analyze the downstream flow field variations for bioprosthetic and mechanical valves under two placement conditions:centralized placement(0 mm)and eccentric placement(1 mm).Hemodynamic parameters such as velocity,vorticity,and viscous shear stress were assessed to evaluate the flow field characteristics.Results By analyzing the flow field variations at four characteristic time points,namely,early systole,acceleration phase,peak systole,and deceleration phase,a significant difference in flow field distribution between bioprosthetic and mechanical valves was observed.The bioprosthetic valve exhibited a centrally symmetric jet with a higher flow velocity,whereas the mechanical valve displayed a three-jet structure with a lower central flow velocity.Under eccentric placement,the blood flow in the aortic sinus region was sluggish,with a reduction in average velocity,hindering the formation and maintenance of vortices.During the peak systolic phase,the maximum viscous shear stresses in the sinus region for the bioprosthetic and mechanical valves were 0.45 and 0.67 Pa,respectively,approaching the threshold for endothelial cell damage.Conclusions Eccentric placement of both mechanical and bioprosthetic valves resulted in reduced sinus blood flow velocity and diminished viscous shear stress,creating favorable conditions for thrombus formation.In clinical practice,careful attention should be given to the placement of valve replacement to prevent eccentric placement.

Objective To investigate the impact of eccentric placement for various types of artificial aortic valves on downstream flow dynamics.Methods A physiological pulsatile circulation simulation system was employed and particle image velocimetry(PIV)was utilized to analyze the downstream flow field variations for bioprosthetic and mechanical valves under two placement conditions:centralized placement(0 mm)and eccentric placement(1 mm).Hemodynamic parameters such as velocity,vorticity,and viscous shear stress were assessed to evaluate the flow field characteristics.Results By analyzing the flow field variations at four characteristic time points,namely,early systole,acceleration phase,peak systole,and deceleration phase,a significant difference in flow field distribution between bioprosthetic and mechanical valves was observed.The bioprosthetic valve exhibited a centrally symmetric jet with a higher flow velocity,whereas the mechanical valve displayed a three-jet structure with a lower central flow velocity.Under eccentric placement,the blood flow in the aortic sinus region was sluggish,with a reduction in average velocity,hindering the formation and maintenance of vortices.During the peak systolic phase,the maximum viscous shear stresses in the sinus region for the bioprosthetic and mechanical valves were 0.45 and 0.67 Pa,respectively,approaching the threshold for endothelial cell damage.Conclusions Eccentric placement of both mechanical and bioprosthetic valves resulted in reduced sinus blood flow velocity and diminished viscous shear stress,creating favorable conditions for thrombus formation.In clinical practice,careful attention should be given to the placement of valve replacement to prevent eccentric placement.

Objective To explore the impact of different moving patterns during the dip-coating process on thickness distributions of polymer heart valves.Methods Based on the volume of fluid(VOF)multiphase flow model,the Eulerian wall-film(EWF)model,and dynamic mesh technology,the dip-coating manufacturing process of polymer heart valves were numerically simulated.The effects of vertical,horizontal,and circular moving patterns on flow characteristics of the surface impregnation liquid and liquid film distributions under self-rotation conditions of the models were mainly studied.Subsequently,seven identical test points were set on each valve leaflet to collect thickness data,and the coefficient of variation(CV)was calculated to evaluate the uniformity of the liquid film thickness.Given that the vertical and horizontal patterns had fewer moving planes,limiting the optimization space,the circular pattern(45°)with richer moving planes was selected as the basis for optimization,and comparative analysis of numerical simulation was conducted.Results In the vertical pattern,the peak CV was 0.461 3;in the horizontal pattern,the CV was 0.060 8;and in the circular pattern,the CV at 30°,45° and 60° were 0.457 5,0.272 8,and 0.255 6,respectively.After optimization,the CV for the circular pattern(45°)decreased to 0.052 5,representing an 80.7％reduction compared to the pre-optimization value.Conclusions The moving patterns significantly affect the uniformity of dip-coating thickness distributions.The horizontal pattern demonstrates the best uniformity,while the vertical pattern shows the poorest uniformity.The CV for the circular pattern decreases as the angle increases,with its uniformity between that of the vertical and horizontal patterns.Optimization of moving pattern parameters based on simulation results has improved the uniformity of thickness distributions.

Objective:To investigate the role of mechanosensor Yes-associated protein 1 (YAP1) in urothelial cells in inducing bladder dysfunction in a partial bladder outlet obstruction (pBOO) model.Methods:Ten female C57BL/6 mice were included in this study and randomly divided into pBOO and sham groups based on body weight using a stratified pairing method, with 5 mice in each group. The pBOO group underwent proximal urethral ligation surgery, while the sham group underwent a sham operation. Two weeks after surgery, the urinary pattern was analyzed using the urine spot test. The significant increase in urine spot numbers indicated the successful establishment of the pBOO model. The mice were then sacrificed, and bladder tissues were weighed and stained with hematoxylin and eosin (HE) to observe morphological changes. The bladder urothelial layer was further isolated, and total cell proteins were extracted to detect the expression levels of YAP1 protein using Western blotting. Mouse immortalized bladder urothelial cells were divided into three experimental groups: the negative control (NC) group, which was treated with YAP1-NC lentivirus; the overexpression (OE) group, which was treated with YAP1-OE lentivirus to induce YAP1 protein overexpression; and the verteporfin treatment (VP) group, which was treated with verteporfin on the basis of the OE group. Real-time quantitative PCR and Western blotting were used to verify the transcription and expression levels of YAP1 protein, the co-transcriptional activator TEAD4 protein, and the phosphorylated protein DRP1-616 (at serine 616) of dynamin-related protein 1 (DRP1). An ATP detection kit was used to measure the ATP release concentration in the NC, OE, and VP groups. The interaction between YAP1 and TEAD4 was investigated using co-immunoprecipitation, and the expression of the mitochondrial marker translocase of the outer mitochondrial membrane 20 (Tom20) was observed using immunofluorescence staining.Results:The results of the urine spot test showed that the number of urine spots on the filter paper in the pBOO group was higher than that in the sham group within 6 hours [(283.0±9.1) spots vs. (3.7±0.3) spots, P<0.01], and the urine spots were scattered. The bladder wet weight in the pBOO group was significantly higher than that in the sham group [(105.70±6.84) mg vs. (22.33±1.20) mg, P<0.01]. Histological observations revealed reduced bladder mucosal folds and increased detrusor muscle thickness in the pBOO group. The expression of YAP1 protein in the bladder urothelial cells of the pBOO group was significantly upregulated compared to the sham group [(1.26±0.08) vs. (0.50±0.04), P<0.01]. In vitro experiments showed that compared to the NC group, the OE group had significantly increased expression of DRP1-616 [(0.94±0.05) vs. (0.33±0.01), P<0.01] and higher ATP release concentration [(24.45±0.16) μmol/mg vs. (19.67±0.42) μmol/mg, P<0.01]. In contrast, the VP group had significantly decreased expression of DRP1-616 [(0.29±0.04) vs. (0.94±0.05), P<0.01] and lower ATP release concentration [(10.55±0.01) μmol/mg vs. (24.45±0.16) μmol/mg, P<0.01] compared to the OE group. Co-immunoprecipitation experiments using YAP1 and TEAD4 antibodies showed that YAP1 and TEAD4 proteins could interact and form a transcriptional complex to regulate ATP release. Immunofluorescence staining revealed increased expression of Tom20 in the OE group compared to the NC group [(104.20±3.28) vs. (74.51±3.87), P<0.01]. Conclusions:In the pBOO-induced bladder dysfunction model, YAP1 is highly expressed in urothelial cells. YAP1 forms a transcriptional complex with TEAD4 to regulate ATP release by promoting mitochondrial fission via DRP1-616 expression, which is a key mechanism underlying pBOO-induced bladder dysfunction.

Objective:To investigate the clinical characteristics of cervical adenocarcinoma and analyze the survival status and related prognostic factors.Methods:The data of 229 patients with cervical adenocarcinoma who were diagnosed pathologically in the General Hospital of Ningxia Medical University from January 2013 to October 2022 were retrospectively analyzed. Among them, 198 early stage patients were mainly treated with surgery, and 31 locally advanced stage patients were mainly treated with chemoradiotherapy. The overall survival (OS) and progression-free survival (PFS) rates in the whole cohort of patients and different treatment subgroups were calculated. Kaplan‐Meier method and log‐rank test were used for survival analysis, and Cox proportional hazards model was used for univariate and multivariate survival analyses.Results:Among the 229 patients, there were 11 subtypes of pathological classifications, predominantly of the usual‐type. At the end of follow‐up, 57 patients (24.9%) relapsed. The 3‐ and 5‐year OS rates were 86.4% and 79.3%, respectively, and the 3‐ and 5‐year PFS rates were 81.6% and 73.6%, respectively. Multivariate analysis showed that International Federation of Gynecology and Obstetrics (FIGO) staging of stages Ⅲ‐Ⅳ was an independent prognostic factor for OS and PFS ( HR=2.033, 95% CI=1.456‐2.839, P<0.001; HR=1.701, 95% CI=1.251‐2.313, P=0.001). Lymph node metastasis was an independent risk factor for PFS ( HR=1.610,95% CI=1.021‐2.539, P=0.041). Subgroup analysis of 198 patients with surgical treatment: the 3‐ and 5‐year OS rates were 90.0% and 84.9%, and the 3‐ and 5‐year PFS rates were 82.7% and 76.7%, respectively. Multivariate analysis showed that lymph node metastasis and deep invasion depth were the main risk factors for OS ( HR=6.893, 95% CI=2.592‐18.327, P<0.001; HR=1.952, 95% CI=1.164‐3.272, P=0.011) and PFS ( HR=5.507, 95% CI=2.569‐11.805, P<0.001; HR=1.638, 95% CI=1.09‐2.461, P=0.018). Ovarian preservation was an independent risk factor for PFS ( HR=3.364, 95% CI=1.115‐10.151, P=0.031). Conclusions:The pathological types of cervical adenocarcinoma are complex and diverse. Local recurrence and distant metastasis are the main reasons for treatment failure. FIGO stage, lymph node metastasis and postoperative depth of invasion are the main prognostic factors of cervical adenocarcinoma.

Objective To analyze the detection of helicobacter pylori(Hp)in different parts of gastric antrum,and to provide clinical guidance for finding the best biopsy site for Hp.Methods Patients who underwent 13C urea breath test and electronic gastroscopy from January 2020 to December 2022 were retrospectively analyzed and divided into 13C urea breath test positive group[delta over baseline(DOB)≥4]and 13C urea breath test negative group(DOB<4)according to DOB value.Gastroscopy reports and pathological data of patients were collected.According to different biopsy sites in gastric antrum,patients were divided into conventional biopsy site group,elevated erosive site group and flat erosive site group,and the detection rate of Hp in different biopsy sites was compared.13C urea breath test positive group was divided into group A(435)according to DOB value,and the gastric antral biopsy and pathology of each group were classified and analyzed.Combined with endoscopic reports and pathological data,patients were divided into atrophic gastritis group and non-atrophic gastritis group.Results In the 13C urea breath test positive group,the detection rate of Hp in the elevated erosive site group(96.4%)was higher than that in the conventional biopsy site group(92.7%)and the flat erosive site group(93.9%),and the difference was statistically significant(P = 0.036).In DOB group A,the detection rate of Hp was the highest at the site of elevated erosive and the lowest at the site of conventional biopsy,and the detection rate of Hp at the three biopsy sites was compared,the difference was statistically significant(P = 0.016);There was no significant difference in the detection rate of Hp at three biopsy sites between group B and group C(P = 0.622;P = 0.721);the non-atrophic gastritis group,the detection rate of Hp at the elevated erosive site(96.5%)was higher than that at the conventional biopsy site(91.2%)and the flat erosive site(92.0%),and the difference was statistically significant(P = 0.043).There was no significant difference in the detection rate of Hp at three biopsy sites in the atrophic gastritis group(P = 0.614).13C urea breath test negative group:There was no significant difference in Hp detection rate among the three biopsy sites(P = 0.255).Conclusion For patients with positive 13C urea breath test but low DOB value,the positive rate of Hp in the elevated erosive site is higher.For non-atrophic gastritis patients,the detection rate of Hp was higher in the elevated erosive sites than in the conventional biopsy sites.But for patients with atrophic gastritis,there was little difference in the detection rate of Hp in different parts of antrum.For patients with negative 13C urea breath test,there was no significant difference in Hp detection rate among the three biopsy sites.In future clinical work,for similar patients,precise biopsy can be performed to improve the detection rate of Hp.