Objective:To explore the possible pharmacodynamic material basis and mechanism of Shaogan Fuzi Decoction in the treatment of rheumatoid arthritis through ultra-high performance liquid chromatography-high-resolution tandem mass spectrometry (UPLC-HRMS/MS) combined with network pharmacology and molecular docking method.Methods:The blood components of Shaogan Fuzi Decoction were analyzed by UPLC-HRMS/MS; the targets of blood components in Shaogan Fuzi Decoction were predicted by PubChem database and Swiss Target Prediction database; DrugBank database, Therapeutic Target Database (TTD) and GeneCards database were used to screen rheumatoid arthritis-related targets, and Venn map of common targets was obtained; the protein interaction network was constructed by STRING database, and the key targets and key components were screened; GO function enrichment analysis and KEGG pathway enrichment analysis were performed by DAVID 6.8 database; the "blood component-target-pathway" network was constructed by Cytoscape 3.2.1 software; Autodock software was used to verify the molecular docking between the predicted key components and key targets in the network.Results:Totally 26 blood components of Shaogan Fuzi Decoction, 526 related targets, 478 related targets of rheumatoid arthritis, and 111 common targets were obtained; the key components such as tangeretin, kaempferol, glycyrrhetinic acid, liquiritigenin, quillaic acid and glabrolide were screened, which acted on key targets such as TNF, IL6, VEGFA, PTGS2, JUN and PPARG. They were mainly involved inflammatory response, steroid metabolic process, response to lipopolysaccharide, extracellular region, cytoplasm, RNA polymerase Ⅱ transcription factor activity, steroid bindingand other biological processes. It mainly regulated steroid hormone biosynthesis, PI3K-Akt signaling pathway, apoptosis, IL-17 signaling pathway, rheumatoid arthritisand other signaling pathways. Molecular docking results showed that the key components had good binding activity with key targets.Conclusion:Shaogan Fuzi Decoction may act on TNF, IL6, VEGFA, PTGS2, JUN, PPARG and other targets through tangeretin, kaempferol, glycyrrhetinic acid and other blood components to regulate PI3K-Akt and other signaling pathways, inhibiting cell proliferation and promoting apoptosis, reducing inflammation, to treat rheumatoid arthritis.

Objective To investigate the effect of pelvic floor stabilized structure preservation (PPSS) during robot-assisted laparoscopic radical prostatectomy (RARP)on postoperative continence recovery.Methods From October 2017 to April 2018,86 patients with prostatic cancer who underwent traditional RARP and RARP plus PPSS were included.There were 31 patients in non-PPSS group and 55 patients in PPSS group.In non-PPSS group,patients age was (68.48 ± 7.79) years old,BMI was (24.79 ± 3.05) kg/m2,median prostate volume was 63.54 (53.00-99.36) cm3,clinic T-stage T1-T2,T3,T4 accounted for 49.39％,22.58％,6.45％ and ISUP grade 1,2,3,4,5 accounted for 22.58％,22.81％,12.90％,12.90％,19.35％ respectively.In PPSS group,patients age was (69.53 ± 6.81)years old,BMI was (23.95 ± 3.03) kg/m2,median prostate volume was 73.39 (54.88-94.23) cm3,clinic T-stage T1-T2,T3,T4 accounted for 72.73％,7.27％,3.64％ and ISUP grade 1,2,3,4,5 accounted for 21.82％,18.18％,23.64％,18.18％,10.91％ respectively.The preoperative PSA,BMI,clinical T-stage,ISUP grade,and postoperative hospital days had no significant differences (P ＞ 0.05)between the two groups.Both groups were operated via transperitoneal approach.In the non PPSS group,endo-pelvic fascia and pubic prostate ligament was cut,and dorsal vessel complex was ligated.In PPSS group,the partial endo-pelvic fascia was bluntly pushed to the pelvic wall to preserve tendon arch,and pubic prostate ligament also was preserved without suturing and ligating dorsal vascular complex.The catheter was removed 7 d after RARP.The continence recovery were compared between the two groups,including pad number on the day of I,7,14,30,90 and ICI-Q-SF scores on the day of 30 and 90 after catheter removal.Results There was no significant difference in pad numbers used between the two groups on the day of 1,7,14,30 after catheter removal.On the 90th day,the proportions of using pad ≥4 in PPSS group were significantly lower than those in non-PPSS group (1.89％ vs.20.69％,P =0.004).No significant difference was found in ICI-Q-SF scores on the 30th and 90th day between the two groups.Univariate analysis showed that PPSS group used less pads than non-PPSS group on the 90th day [OR =0.07(95％ CI 0.01-0.65),P =0.019];T3 patients used more pads than T1-T2 patients [OR =9.19 (95％ CI 1.32-63.87),P =0.025].After adjusting for age,ISUP grading,T staging,and PSA,multivariate regression analysis showed that the risk of using pad ≥ 4 in PPSS group compared with non-PPSS group was 0.46,0.34,0.27,0.25,and 0.03 on the day of 1,7,14,30 and 90 after catheter removal,respectively.The PPSS approach didn't increase the risk of positive surgical margin.Conclusions Preservation of pelvic stabilized structure in RARP is very efficient in term of continence rate after RARP,and it does not increase the risk of positive surgical margin.

Objectives:To examine the functional outcomes of robot-assisted radical prostatectomy (RARP) with preservation of pelvic floor stabilized structure and early elevated retrograde liberation of the neurovascular bundle (PEEL).Methods:This study was a retrospective cohort study. Between June 1, 2022, and March 20, 2023, 27 cases of RARP with PEEL and 153 cases of RARP with preservation of pelvic floor stabilized structure (PPSS) were included in this study. All patients were males, aged (62.5±5.2) years (range: 50 to 73 years). There were 18 cases of ≤T2b stage and 9 cases of T2c stage. After 1∶1 propensity score matching, the postoperative functional outcomes of 27 cases of RARP with PEEL and 27 cases of RARP with PPSS were compared. All surgeries were performed by a single surgeon and included patients were clinically staged as cT1-2N0M0 without preoperative urinary incontinence or erectile dysfunction. In RARP with PEEL, the prostate was cut near the midline at the front when dissecting the neurovascular bundle, dissection was performed between the visceral layer of the pelvic fascia and the prostatic fascia, preserving the parietal layer and the visceral layer of the pelvic fascia, and the neurovascular bundle was retrogradely released from the apex. The cumulative probability curve was plotted using the Kaplan-Meier method and the Log-rank test was used to compare the differences in functional outcomes between the two groups. Univariate and multivariate analysis with the Cox proportional hazards model was used to compare postoperative urinary continence and sexual function.Results:The recovery time of continence and potency was significantly longer in the PPSS group than in the PEEL group (all P<0.05). The continence rate of the PEEL group was significantly higher than that of the PPSS group (92.59% vs. 68.10%, P=0.026) at 3 months after surgery. The potency rate of the PEEL group was also significantly higher than that of the PPSS group (40.70% vs. 15.10%, P=0.037) at 3 months after surgery. In the univariate analysis, compared to the PPSS technique, the PEEL technique was associated with a shorter recovery time of continence ( HR=1.94, 95% CI: 1.08 to 3.48, P=0.027) and a shorter recovery time of potency ( HR=2.06, 95% CI: 1.03 to 4.13, P=0.042). In the multivariate analysis, the PEEL technique was an independent prognosis factor for postoperative recovery of continence ( HR=2.05, 95% CI: 1.01 to 4.17, P=0.047) and potency ( HR=3.57, 95% CI: 1.43 to 8.92, P=0.007). All the cases of the PPSS group and the PEEL group were performed successfully with negative surgical margins. Conclusion:Compared with PPSS, PEEL may be more conducive to the recovery of urinary continence and sexual function after RARP.

Objectives:To examine the functional outcomes of robot-assisted radical prostatectomy (RARP) with preservation of pelvic floor stabilized structure and early elevated retrograde liberation of the neurovascular bundle (PEEL).Methods:This study was a retrospective cohort study. Between June 1, 2022, and March 20, 2023, 27 cases of RARP with PEEL and 153 cases of RARP with preservation of pelvic floor stabilized structure (PPSS) were included in this study. All patients were males, aged (62.5±5.2) years (range: 50 to 73 years). There were 18 cases of ≤T2b stage and 9 cases of T2c stage. After 1∶1 propensity score matching, the postoperative functional outcomes of 27 cases of RARP with PEEL and 27 cases of RARP with PPSS were compared. All surgeries were performed by a single surgeon and included patients were clinically staged as cT1-2N0M0 without preoperative urinary incontinence or erectile dysfunction. In RARP with PEEL, the prostate was cut near the midline at the front when dissecting the neurovascular bundle, dissection was performed between the visceral layer of the pelvic fascia and the prostatic fascia, preserving the parietal layer and the visceral layer of the pelvic fascia, and the neurovascular bundle was retrogradely released from the apex. The cumulative probability curve was plotted using the Kaplan-Meier method and the Log-rank test was used to compare the differences in functional outcomes between the two groups. Univariate and multivariate analysis with the Cox proportional hazards model was used to compare postoperative urinary continence and sexual function.Results:The recovery time of continence and potency was significantly longer in the PPSS group than in the PEEL group (all P<0.05). The continence rate of the PEEL group was significantly higher than that of the PPSS group (92.59% vs. 68.10%, P=0.026) at 3 months after surgery. The potency rate of the PEEL group was also significantly higher than that of the PPSS group (40.70% vs. 15.10%, P=0.037) at 3 months after surgery. In the univariate analysis, compared to the PPSS technique, the PEEL technique was associated with a shorter recovery time of continence ( HR=1.94, 95% CI: 1.08 to 3.48, P=0.027) and a shorter recovery time of potency ( HR=2.06, 95% CI: 1.03 to 4.13, P=0.042). In the multivariate analysis, the PEEL technique was an independent prognosis factor for postoperative recovery of continence ( HR=2.05, 95% CI: 1.01 to 4.17, P=0.047) and potency ( HR=3.57, 95% CI: 1.43 to 8.92, P=0.007). All the cases of the PPSS group and the PEEL group were performed successfully with negative surgical margins. Conclusion:Compared with PPSS, PEEL may be more conducive to the recovery of urinary continence and sexual function after RARP.

Background::Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a microbarrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.Methods::The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models. Results::Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.Conclusions::The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.

Aim To explore the feasibility of using machine learning algorithms combined with coronary computed tomography(CT)derived perivascular fat attenuation index(FAI)and plaque information to evaluate myocardial ischemia in stable coronary heart disease patients.Methods A retrospective analysis was conducted on the clinical and imaging data of patients who underwent preoperative coronary CT angiography(CCTA),invasive coronary angiography(ICA),and flow reserve fraction(FFR)measurements at Zhongshan Hospital Affiliated to Fudan University from April 2019 to October 2021.206 patients with stable coronary heart disease were selected.The semi-automatic plaque analysis software was used for quantification of plaque and lumen parameters and perivascular FAI measurement,with man-ual delineation of a 40 mm segment of the coronary artery starting 10 mm from the ostium for perivascular FAI measure-ment.Differences in plaque characteristics,perivascular FAI,and coronary perivascular FAI between stable coronary heart disease patients with FFR≤0.8 and FFR＞0.8 were compared.The diagnostic performance of combining perivascu-lar FAI,coronary perivascular FAI,and plaque features using machine learning algorithms for myocardial ischemia in stable coronary heart disease patients was evaluated through ROC curves.Results 206 stable coronary heart disease patients were divided into FFR≤0.8 group(50 cases)and FFR＞0.8 group(156 cases).The mean periplaque FAI of patients with FFR≤0.8 was-69.28±5.65 HU,significantly higher than that of patients with FFR＞0.8 at-80.10±7.75 HU(P＜0.001).Further analysis was conducted using machine learning models,including XGBoost,random forest,and Logistic regression models,all of which had an accuracy rate of over 0.8 in diagnosing myocardial ischemia.Among them,the XGBoost model performed the best with an accuracy of 0.903,an F1 value of 0.774,and an AUC of 0.931,in-dicating its high effectiveness in diagnosing myocardial ischemia.Conclusion The combination of FAI and machine learning algorithm XGBoost model is a new method for diagnosing myocardial ischemia,which has better diagnostic value in evaluating myocardial ischemia in stable coronary heart disease patients.

AIM:To observe the therapeutic efficacy of 25G+minimally invasive vitrectomy for retinal arterial macroaneurysm.METHODS:Totally 40 patients(40 eyes)who admitted to Jinan Mingshui Eye Hospital from January 2021 to May 2024 and with vitreous hemorrhage or dense premacular hemorrhage in the macular area caused by retinal arterial macroaneurysm, underwent 25G+minimally invasive vitrectomy. Preoperative and postoperative best-corrected visual acuity(BCVA), complications, and special cases were analyzed.RESULTS: The general patient data aligned with previous literature reports. The postoperative BCVA was significantly improved(t=9.72, P<0.01), and no significant serious surgical complications were observed. Notably, intraoperative findings revealed secondary macular holes in 3 eyes, resulting in poor visual prognosis.CONCLUSION: For vitreous hemorrhage or dense premacular hemorrhage caused by retinal arterial macroaneurysm, 25G+ minimally invasive vitrectomy is a safe and effective treatment. Visual prognosis was excluded for secondary macular holes.