[Objective] To analyze the prognostic value of prostate cancer (PCa) pyroptosis-related genes (PRGs) using gene expression databases and to explore the regulatory mechanism of nucleotidebinding oligomerization domain-like receptor containing pyrin domain 1 (NLRP1) in the pyroptosis of PCa cells. [Methods] Fragments per kilobase of exon model per million reads mapped (FPKM) data and clinical information from PCa and adjacent tissues from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were obtained. Differentially expressed PRGs between PCa and adjacent tissues, classified subtypes and plotted survival curves were analyzed. Univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO) regression analysis were conducted to screen prognosis-related PRGs, risk scores were calculated, and a prognostic risk model was constructed and validated. Patients were divided into high and low risk groups based on the median risk scores from the training and validation sets, and gene ontology (GO) enrichment and kyoto encyclopedia of genes and genomes (KEGG) analysis were conducted on differentially expressed PRGs. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of NLRP1 in PCa cell lines, and pyroptosis was induced in DU145 and LNCaP cells while morphological changes were observed. Western blot (WB) was performed to detect the expression of pyroptosis-related molecules. [Results] A total of 6 prognostic-related PRGs were obtained, including CHMP4C, CYCS, GPX4, GSDMB, NLRP1, and PLCG1. The risk score was positively correlated with the risk of recurrence but negatively correlated with the progression-free survival (P<0.001). The area under the receiver operating characteristic curves (AUCs) for the training set at 1, 3, and 5 years were 0.769 (95%CI: 0.652-0.878), 0.804 (95%CI: 0.736-0.882), and 0.772 (95%CI: 0.631-0.905), respectively, while those for the validation set were 0.731 (95%CI: 0.647-0.826), 0.753 (95%CI: 0.674-0.818), and 0.763 (95%CI: 0.626-0.849), respectively. Differences in expression levels of the 6 PRGs were observed between the high and low risk groups in both the training and validation sets (P<0.05). Cox regression analysis showed that T stage, prostate specific antigen (PSA), Gleason grade, and risk score were independent predictors of PCa prognosis (P<0.05). Differences in risk scores were observed among patients of different ages, T stages, and Gleason grades (P<0.05). NLRP1 was found to be lowly expressed in PCa cell lines and was involved in the regulation of pyroptosis in DU145 and LNCaP cells. [Conclusion] The prognostic risk model constructed based on PRGs has a certain predictability for the prognosis of PCa patients, and NLRP1 may be involved in the regulation of pyroptosis in PCa cells.

Objective:To explore the clinical characteristics of adrenal lesions in unilateral primary aldosteronism.Methods:This is a prospective study. Consecutive patients diagnosed with unilateral primary aldosteronism at the First Affiliated Hospital of Chongqing Medical University from December 2023 to November 2024 were included. Inclusion criteria：① Age is 18 to 80 years old；② The laboratory test indicators are in line with the diagnosis of primary aldosteronism；③ The auxiliary examination proved that only one side was involved；④ Patient undergo unilateral total adrenalectomy. The exclusion criteria are as follows：① Complete biochemical remission was not achieved during the 1-6 month follow-up after the surgery；② Postoperative loss to follow-up；③ No surgical specimens were received or the surgical specimens were incomplete，making continuous sectioning impossible. Patients meeting the inclusion criteria were recruited，and their clinical and biochemical data were recorded. The number of adrenal nodules visible on CT scans and the number of macroscopically visible nodules in the postoperative adrenal gross specimens were documented. Hematoxylin-eosin（HE）staining and aldosterone synthase CYP11B2 immunohistochemical staining were performed on the adrenal tissues after the operation. The number of nodules visible under the light microscope and the number of CYP11B2-positive nodules were recorded.Results:A total of 114 cases were included in this study. The age of the patients was（49.86 ± 9.80）years，the body mass index was（25.49 ± 3.40）kg/m2，the preoperative aldosterone level was 352（2012，556）pg/ml，and the direct renin concentration was 1.63（0.50，4.56）μIU/ml. The aldosterone/renin ratio was 224.9（57.1，641.6）（aldosterone concentration unit was pg/ml，renin concentration unit was μIU/ml），the minimum blood potassium concentration was 2.87（2.50，3.40）mmol/L，and the systolic blood pressure was（144.5 ± 19.5）mmHg. Among the 114 patients，105 had adrenal nodules detected by preoperative CT，of whom 2（1.75%）had multiple nodules. Postoperative gross adrenal specimen evaluation and CYP11B2 immunohistochemical staining revealed that 90 out of 114 cases were solitary nodules，2 cases had no nodules，and 22 cases（19.30%）had multiple nodules detected（17 cases had 2 nodules and 5 cases had 3 nodules）. Among them，12 cases（10.53%）presented as grossly visible multinodular lesions，while 10 cases（8.77%）appeared as solitary nodules macroscopically but demonstrated multinodular patterns on immunohistochemical staining. CYP11B2 staining showed that among the 22 patients with multiple nodules，13 had multiple CYP11B2-positive nodules，while the remaining had only one positive nodule. Among the 22 patients with multiple nodules，preoperative CT showed single nodules in 19 cases，hyperplasia in 1 case，and multiple nodules in 2 cases（9.09%）. Among the 12 patients with grossly visible multinodular lesions，preoperative CT showed single nodules in 9 cases，hyperplasia in 1 case，and multiple nodules in 2 cases（16.67%）.Conclusions:Multiple adrenal nodules associated with unilateral primary aldosteronism are relatively common，and are often not detected by preoperative CT examination. Partial adrenalectomy based solely on CT-visible nodules may fail to achieve complete remission of primary aldosteronism. This study provides evidence supporting total adrenalectomy as the preferred surgical approach for unilateral primary aldosteronism.

Objective·To fabricate a 3D-printed dental crown and bridge resin slurry using digital light processing(DLP)technology,investigate the influence of different printing parameters on its mechanical properties,determine the optimal printing parameters,and optimize the composition ratio of DLP-printed crown and bridge resin.Methods·Based on the viscosity characteristics of the mixture,the optimal ratio of urethane dimethacrylate(UDMA)to poly(propylene glycol)dimethacrylate(PPGDMA)was explored.After silanizing silicon dioxide(SiO2),it was mixed with UDMA,PPGDMA,and 2,4,6-trimethylbenzoyl bis(p-tolyl)phosphine oxide(TMO)to prepare DLP-printed dental crown and bridge resin slurries with different solid contents,and their rheological properties were tested.The Beer-Lambert equation was used to calculate the light penetration depth and critical exposure energy of the printing slurry.Based on these values,different exposure intensities,exposure times,post-curing times,and layer thicknesses were set respectively to carry out a series of printing experiments.By comparing and analyzing the flexural strength of the products under different printing parameters,the optimal printing parameter combination was screened out.Results·Viscosity tests showed that the optimal UDMA-to-PPGDMA ratio was 6∶4.The rheological behavior of printing slurries with different solid contents was tested,and the results showed that the DLP-printed dental crown and bridge resin with a solid content of 22%exhibited the best printing performance.According to the Beer-Lambert analysis,the light penetration depth Dp of the printing slurry was 119.79 μm,and the critical exposure energy Ec was 25.54 mJ/cm2.When the exposure intensity was 20 mW/cm2,the flexural strength reached a maximum of(132.39±8.92)MPa,and the difference was statistically significant(P<0.05).The flexural results of different exposure times showed that the flexural strength could reach(131.73±9.43)MPa when the single-layer exposure time was 3.0 s,and there was no significant difference when the exposure time was further increased.The flexural results of different post-curing times showed that when the post-curing time reached 30 min,there was no significant relationship between the flexural strength value and the increase in post-curing time.Regarding the influence of different layer thicknesses on the flexural performance,the test results showed that when the layer thickness was 50 μm,the result was the best,and the difference was statistically significant(P<0.001).Conclusion·Based on viscosity and rheological tests,a DLP-printable crown and bridge resin slurry was successfully developed.The optimal printing parameters were determined through statistical analysis of flexural strength:exposure intensity of 20 mW/cm2,exposure time of 3.0 s,post-curing time of 30 min,and a layer thickness of 50 μm.

Objective:To evaluate the effect of preoperative anxiety on the consciousness and autonomic nervous activity during propofol anesthesia.Methods:This study was a secondary analysis of data from the clinical trial in a prospective single-arm study. One hundred and thirty patients, aged 18-65 yr, with a body mass index of 18.5-27.9 kg/m 2, of American Society of Anesthesiologists Physical Status classification I or Ⅱ, scheduled to receive propofol anesthesia, were selected from the Second People′s Hospital of Lianyungang. The six-item of the state anxiety inventory (SAI) of the State-Trait Anxiety Inventory was used to assess the anxiety of patients 1 h before surgery. The patients were divided into 2 groups according to the cut-off value of 12: obvious anxiety symptom (SAI score >12) group (group A, n=49) and no obvious anxiety symptom (SAI score ≤12) group (group B, n=81). After admission to the operating room, the patient was required to hold a 50 ml syringe filled with water. Propofol was given by target-controlled infusion (TCI) with the target plasma concentration set at 5 μg/ml. When the effect-site concentration (Ce) of propofol increased to 3.5 μg/ml (all the patients lost consciousness), the closed-loop TCI was used to maintain BIS value between 45 and 55. The patients were monitored for 20 min after stopping the pump infusion (anesthesia recovery period). The disappearance time of verbal command, disappearance time of eyelash reflex, time of syringe dropping, recovery time of verbal command, recovery time of eyelash reflex, Ce at the recovery of verbal command, Ce at the recovery of eyelash reflex, Ce within the first 5 min of the closed-loop TCI, and consumption of propofol during anesthesia were recorded. The peripheral perfusion index, low frequency power and high frequency power of heart rate variability were recorded, and the ratio of low frequency power to high frequency power was calculated. Pearson correlation analysis was used to assess the correlation between preoperative SAI score and consciousness-related indicators, simulated Ce of propofol and consumption of propofol. Results:Compared with group B, the disappearance time of verbal command, disappearance time of eyelash reflex, and time of syringe dropping were significantly prolonged, the consumption of propofol, simulated Ce at recovery of verbal command and within the first 5 min of closed-loop TCI were increased, the peripheral perfusion index was decreased at each time point before administration and at 14-20 min of anesthesia recovery, and the low-frequency power was decreased during anesthesia maintenance in group A ( P<0.05). The SAI score was positively correlated with the disappearance time of verbal command ( r=0.220, P=0.012), time of syringe dropping ( r=0.206, P=0.029), consumption of propofol ( r=0.330, P<0.001), and the simulated Ce at the recovery of verbal command ( r=0.215, P=0.015) and simulated Ce at recovery of eyelash reflex ( r=0.207, P=0.022). Conclusions:Preoperative anxiety may lead to prolonged loss of consciousness and more marked inhibition of sympathetic nerve activity during propofol anesthesia.

Objective·To fabricate a 3D-printed dental crown and bridge resin slurry using digital light processing(DLP)technology,investigate the influence of different printing parameters on its mechanical properties,determine the optimal printing parameters,and optimize the composition ratio of DLP-printed crown and bridge resin.Methods·Based on the viscosity characteristics of the mixture,the optimal ratio of urethane dimethacrylate(UDMA)to poly(propylene glycol)dimethacrylate(PPGDMA)was explored.After silanizing silicon dioxide(SiO2),it was mixed with UDMA,PPGDMA,and 2,4,6-trimethylbenzoyl bis(p-tolyl)phosphine oxide(TMO)to prepare DLP-printed dental crown and bridge resin slurries with different solid contents,and their rheological properties were tested.The Beer-Lambert equation was used to calculate the light penetration depth and critical exposure energy of the printing slurry.Based on these values,different exposure intensities,exposure times,post-curing times,and layer thicknesses were set respectively to carry out a series of printing experiments.By comparing and analyzing the flexural strength of the products under different printing parameters,the optimal printing parameter combination was screened out.Results·Viscosity tests showed that the optimal UDMA-to-PPGDMA ratio was 6∶4.The rheological behavior of printing slurries with different solid contents was tested,and the results showed that the DLP-printed dental crown and bridge resin with a solid content of 22%exhibited the best printing performance.According to the Beer-Lambert analysis,the light penetration depth Dp of the printing slurry was 119.79 μm,and the critical exposure energy Ec was 25.54 mJ/cm2.When the exposure intensity was 20 mW/cm2,the flexural strength reached a maximum of(132.39±8.92)MPa,and the difference was statistically significant(P<0.05).The flexural results of different exposure times showed that the flexural strength could reach(131.73±9.43)MPa when the single-layer exposure time was 3.0 s,and there was no significant difference when the exposure time was further increased.The flexural results of different post-curing times showed that when the post-curing time reached 30 min,there was no significant relationship between the flexural strength value and the increase in post-curing time.Regarding the influence of different layer thicknesses on the flexural performance,the test results showed that when the layer thickness was 50 μm,the result was the best,and the difference was statistically significant(P<0.001).Conclusion·Based on viscosity and rheological tests,a DLP-printable crown and bridge resin slurry was successfully developed.The optimal printing parameters were determined through statistical analysis of flexural strength:exposure intensity of 20 mW/cm2,exposure time of 3.0 s,post-curing time of 30 min,and a layer thickness of 50 μm.

Objective:To evaluate the effect of preoperative anxiety on the consciousness and autonomic nervous activity during propofol anesthesia.Methods:This study was a secondary analysis of data from the clinical trial in a prospective single-arm study. One hundred and thirty patients, aged 18-65 yr, with a body mass index of 18.5-27.9 kg/m 2, of American Society of Anesthesiologists Physical Status classification I or Ⅱ, scheduled to receive propofol anesthesia, were selected from the Second People′s Hospital of Lianyungang. The six-item of the state anxiety inventory (SAI) of the State-Trait Anxiety Inventory was used to assess the anxiety of patients 1 h before surgery. The patients were divided into 2 groups according to the cut-off value of 12: obvious anxiety symptom (SAI score >12) group (group A, n=49) and no obvious anxiety symptom (SAI score ≤12) group (group B, n=81). After admission to the operating room, the patient was required to hold a 50 ml syringe filled with water. Propofol was given by target-controlled infusion (TCI) with the target plasma concentration set at 5 μg/ml. When the effect-site concentration (Ce) of propofol increased to 3.5 μg/ml (all the patients lost consciousness), the closed-loop TCI was used to maintain BIS value between 45 and 55. The patients were monitored for 20 min after stopping the pump infusion (anesthesia recovery period). The disappearance time of verbal command, disappearance time of eyelash reflex, time of syringe dropping, recovery time of verbal command, recovery time of eyelash reflex, Ce at the recovery of verbal command, Ce at the recovery of eyelash reflex, Ce within the first 5 min of the closed-loop TCI, and consumption of propofol during anesthesia were recorded. The peripheral perfusion index, low frequency power and high frequency power of heart rate variability were recorded, and the ratio of low frequency power to high frequency power was calculated. Pearson correlation analysis was used to assess the correlation between preoperative SAI score and consciousness-related indicators, simulated Ce of propofol and consumption of propofol. Results:Compared with group B, the disappearance time of verbal command, disappearance time of eyelash reflex, and time of syringe dropping were significantly prolonged, the consumption of propofol, simulated Ce at recovery of verbal command and within the first 5 min of closed-loop TCI were increased, the peripheral perfusion index was decreased at each time point before administration and at 14-20 min of anesthesia recovery, and the low-frequency power was decreased during anesthesia maintenance in group A ( P<0.05). The SAI score was positively correlated with the disappearance time of verbal command ( r=0.220, P=0.012), time of syringe dropping ( r=0.206, P=0.029), consumption of propofol ( r=0.330, P<0.001), and the simulated Ce at the recovery of verbal command ( r=0.215, P=0.015) and simulated Ce at recovery of eyelash reflex ( r=0.207, P=0.022). Conclusions:Preoperative anxiety may lead to prolonged loss of consciousness and more marked inhibition of sympathetic nerve activity during propofol anesthesia.

Objective:To explore the clinical characteristics of adrenal lesions in unilateral primary aldosteronism.Methods:This is a prospective study. Consecutive patients diagnosed with unilateral primary aldosteronism at the First Affiliated Hospital of Chongqing Medical University from December 2023 to November 2024 were included. Inclusion criteria：① Age is 18 to 80 years old；② The laboratory test indicators are in line with the diagnosis of primary aldosteronism；③ The auxiliary examination proved that only one side was involved；④ Patient undergo unilateral total adrenalectomy. The exclusion criteria are as follows：① Complete biochemical remission was not achieved during the 1-6 month follow-up after the surgery；② Postoperative loss to follow-up；③ No surgical specimens were received or the surgical specimens were incomplete，making continuous sectioning impossible. Patients meeting the inclusion criteria were recruited，and their clinical and biochemical data were recorded. The number of adrenal nodules visible on CT scans and the number of macroscopically visible nodules in the postoperative adrenal gross specimens were documented. Hematoxylin-eosin（HE）staining and aldosterone synthase CYP11B2 immunohistochemical staining were performed on the adrenal tissues after the operation. The number of nodules visible under the light microscope and the number of CYP11B2-positive nodules were recorded.Results:A total of 114 cases were included in this study. The age of the patients was（49.86 ± 9.80）years，the body mass index was（25.49 ± 3.40）kg/m2，the preoperative aldosterone level was 352（2012，556）pg/ml，and the direct renin concentration was 1.63（0.50，4.56）μIU/ml. The aldosterone/renin ratio was 224.9（57.1，641.6）（aldosterone concentration unit was pg/ml，renin concentration unit was μIU/ml），the minimum blood potassium concentration was 2.87（2.50，3.40）mmol/L，and the systolic blood pressure was（144.5 ± 19.5）mmHg. Among the 114 patients，105 had adrenal nodules detected by preoperative CT，of whom 2（1.75%）had multiple nodules. Postoperative gross adrenal specimen evaluation and CYP11B2 immunohistochemical staining revealed that 90 out of 114 cases were solitary nodules，2 cases had no nodules，and 22 cases（19.30%）had multiple nodules detected（17 cases had 2 nodules and 5 cases had 3 nodules）. Among them，12 cases（10.53%）presented as grossly visible multinodular lesions，while 10 cases（8.77%）appeared as solitary nodules macroscopically but demonstrated multinodular patterns on immunohistochemical staining. CYP11B2 staining showed that among the 22 patients with multiple nodules，13 had multiple CYP11B2-positive nodules，while the remaining had only one positive nodule. Among the 22 patients with multiple nodules，preoperative CT showed single nodules in 19 cases，hyperplasia in 1 case，and multiple nodules in 2 cases（9.09%）. Among the 12 patients with grossly visible multinodular lesions，preoperative CT showed single nodules in 9 cases，hyperplasia in 1 case，and multiple nodules in 2 cases（16.67%）.Conclusions:Multiple adrenal nodules associated with unilateral primary aldosteronism are relatively common，and are often not detected by preoperative CT examination. Partial adrenalectomy based solely on CT-visible nodules may fail to achieve complete remission of primary aldosteronism. This study provides evidence supporting total adrenalectomy as the preferred surgical approach for unilateral primary aldosteronism.

Objective:To investigate the distribution of pathological types of unilateral primary aldosteronism, and to explore the clinical characteristics and prognosis of patients with different pathological types.Methods:A total of 241 patients with unilateral primary aldosteronism who underwent adrenal surgery were included in this study. The clinical data and postoperative follow-up data were collected, and the postoperative tissue sections were stained with HE and aldosterone synthase. According to the staining results, pathological types of 241 patients were classified, and the clinical characteristics and surgical prognosis of patients with unilateral primary aldosteronism were compared.Results:According to the international histopathology consensus for unilateral primary aldosteronism, among 241 patients with unilateral primary aldosteronism, 223 were classical(92.5%), 17 were non-classical(7.1%), and 1 was aldosterone producing carcinoma(0.4%). Among classical cases, 189 were aldosterone producing adenoma and 34 were aldosterone producing nodule. In the non-classical cases, 8 cases were multiple aldosterone producing nodule and 9 cases were multiple aldosterone producing nodule. Compared with the classical group, the non-classical group had a longer duration of hypertension(9.0 vs 5.0 years, P=0.062) and a lower baseline plasma aldosterone concentration(273 vs 305 pg/mL, P=0.147), but the difference was not significant. There was no significant difference between the two groups in the proportion of patients who achieved a complete biochemical response after surgery(98% vs 92.3%, P=0.281), but the proportion of patients who achieved a complete clinical response was significantly lower in the non-classical group(23.1% vs 52.9%, P=0.046). Conclusion:The pathological types of unilateral primary aldosteronism are predominantly classical, with aldosterone-producing adenoma being the most common. There were no significant differences in the clinical characteristics and postoperative biochemical remission rates between classical and non-classical patients, but the clinical prognosis of the latter was inferior to the former.

Primary aldosteronism(PA) is one of the most common secondary hypertension, the pathogenesis is still not fully understood. Aldosterone synthase(CYP11B2) was thought to be continuously expressed in the zona glomerulosa of the adrenal cortex. In recent years, it is found that there were discontinuous CYP11B2 positive cell clusters in adrenal cortex via immunohistochemical staining, and proposed the concept of aldosterone-producing cell clusters(APCC). Thenceforwarding a growing body of studies suggest that there may be a potential causal link between APCC and PA. This article summarizes the latest studies on APCC and provide an update on the potential role of APCC in the pathogenesis of PA.

Macrophages play critical roles in renal fibrosis. However, macrophages exhibit ontogenic and functional heterogeneities, and which population of macrophages contributes to renal fibrosis and the underlying mechanisms remain unclear. In this study, we genetically targeted Notch signaling by disrupting the transcription factor recombination signal binding protein-Jκ (RBP-J), to reveal its role in regulation of macrophages during the unilateral ureteral obstruction (UUO)-induced murine renal fibrosis. Myeloid-specific disruption of RBP-J attenuated renal fibrosis with reduced extracellular matrix deposition and myofibroblast activation, as well as attenuated epithelial-mesenchymal transition, likely owing to the reduced expression of TGF-β. Meanwhile, RBP-J deletion significantly hampered macrophage infiltration and activation in fibrotic kidney, although their proliferation appeared unaltered. By using macrophage clearance experiment, we found that kidney resident macrophages made negligible contribution, but bone marrow (BM)-derived macrophages played a major role in renal fibrogenesis. Further mechanistic analyses showed that Notch blockade reduced monocyte emigration from BM by down-regulating CCR2 expression. Finally, we found that myeloid-specific Notch activation aggravated renal fibrosis, which was mediated by CCR2 macrophages infiltration. In summary, our data have unveiled that myeloid-specific targeting of Notch could ameliorate renal fibrosis by regulating BM-derived macrophages recruitment and activation, providing a novel strategy for intervention of this disease.