OBJECTIVE: In order to enhance the efficacy of anti-breast cancer, paclitaxel nanoparticles (PTX NPs) and polypyrrole nanoparticles (PPy NPs) were combined with photothermal therapy and chemotherapy. At the same time, the two dosage forms of PTX NPs and PTX NPs gel were compared. METHODS: PTX NPs were prepared by self-assembly method, and then the cytotoxicity in vitro was investigated by Methyl thiazolyl tetrazolium (MTT) and other methods, and the efficacy and side effects in vivo were further investigated. RESULTS: The average hydrated diameter, PDI and electric potential of PTX NPs were (210.20 ± 1.57) nm, (0.081 ± 0.003) mV and (15.80 ± 0.35) mV, respectively. MTT results showed that the IC₅₀ value of PTX NPs on 4 T1 cells was 0.490 μg/mL, while that of PTX injection was 1.737 μg/mL. The cell inhibitory effect of PTX NPs was about 3.5 times higher than that of PTX injection. The tumor inhibition rates of PTX NPs and gel were 48.64% and 56.79%, respectively. Together with local photothermal stimulation, the tumor inhibition rate of the PTX NPs reached 91.05%, surpassing that of the gel under the same conditions (48.98%), moreover, the organ index and H&E staining results of PTX NPs showed a decrease in toxicity. CONCLUSION This combination therapy can significantly enhance the effect of anti-breast cancer, and the synergistic effect of chemotherapy and light and heat provides a feasible and effective strategy for the treatment of tumor.

[Purpose]To analyze and evaluate the application effect of quantitative fecal immuno-chemical test(FIT)in the opportunistic screening of colorectal cancer(CRC)in health examination population.[Methods]10 025 healthy individuals who completed quantitative FIT at the Health Management Cancer of Sichuan Cancer Hospital from January 1,2021 to December 31,2023 were included.Participants with positive FIT results were recommended for diagnostic colonoscopy.Quantitative FIT positivity rate,colonoscopy screening compliance rate,and colorectal lesion de-tection rate in the queue population were analyzed,the detection rate of colorectal lesions and colonoscopy resource load between quantitative FIT positive and negative colonoscopy screening groups at all levels were compared and the diagnostic efficacy of quantitative FIT for non progres-sive lesions and progressive lesions were explored.[Results]The positive rate of quantitative FIT was 6.24％(95％CI:5.77％～6.71％).The compliance rate of colonoscopy screening was 20.93％(95％CI:17.74％～24.12％).Among 284 colonoscopy patients,7 cases were detected with CRC,21 cases with advanced adenomas,52 cases with non advanced adenomas,40 cases with non adenomatous polyps,51 cases with other benign lesions,and 113 cases without abnormalities.The detection rates of non advanced adenomas,advanced adenomas,colorectal cancer,non pro-gressive lesions and progressive lesions in the quantitative FIT positive group were significantly higher than those in the quantitative FIT negative group.The detection rates of those without obvi-ous abnormalities were significantly lower than those in the quantitative FIT negative group,and the differences were statistically significant(all P＜0.05).The resource burden of colonoscopy in the quantitative FIT positive and negative groups was 5.46(95％CI:1.56～9.34)and 38.25(95％CI:30.55～45.95),respectively.The level of FIT measurement gradually increases with the severity of the lesion,and the difference between groups is statistically significant(H=48.308,P＜0.001).Quan-titative FIT has high sensitivity and negative predictive value for non progressive lesions and pro-gressive lesions,with values of 71.15％,85.71％and 90.20％,97.39％,respectively.The AUC values for quantitative FIT screening of non progressive lesions and progressive lesions were 0.653(95％CI:0.572～0.734,P=0.001)and 0.720(95％CI:0.631～0.808,P＜0.001),respectively.[Conclusion]Quantitative FIT,as a suitable technique for CRC opportunistic screening in health check-up population,has good diagnostic efficacy for non progressive lesions and progressive le-sions.Performing colonoscopy on FIT positive individuals can improve lesion detection rates while reducing colonoscopy resource consumption,aligning with China's healthcare resource landscape.

Objective·To investigate the role and mechanism of sirtuin 5(SIRT5)in pulmonary microvascular endothelial cell injury in sepsis.Methods·Wild-type(WT)and Sirt5 gene knockout C57BL/6 male mice underwent cecal ligation and puncture(CLP)surgery.Following euthanasia,lung tissues were collected.Pulmonary inflammation was assessed using hematoxylin and eosin(H-E)staining;vascular leakage was evaluated by Evans blue(EB)staining;coagulation function in mice was analyzed via immunofluorescence staining of lung tissues.Immunohistochemical staining was employed to detect vascular cell adhesion molecule-1(VCAM-1)protein expression,thereby assessing endothelial inflammation in CLP-treated mice.By using gene editing technology,SIRT5 was knocked down or overexpressed in human umbilical vein endothelial cells(HUVECs),and the cells were subsequently stimulated with lipopolysaccharide(LPS)to induce endothelial inflammation.Protein expression levels of VCAM-1,tissue factor(TF),and other endothelial injury markers were detected by Western blotting,and inflammatory cytokines such as interleukin-6(IL-6)and IL-1β,were detected by quantitative real-time PCR(qPCR).In addition,transcriptomic sequencing was performed on HUVECs overexpressing SIRT5,and key genes including F2R-like thrombin or trypsin receptor 3(F2RL3),serpin family A member 3(SERPINA3),and transforming growth factor β2/β3(TGF-β2/3)were validated by qPCR.Results·Sirt5 knockout significantly aggravated lung injury in CLP mice,reducing their survival rates(P<0.001).H-E staining showed increased inflammatory infiltration in the lung tissue of the mice,while EB staining indicated increased vascular leakage(P<0.001).Immunofluorescence revealed elevated fibrinogen deposition.In HUVECs with SIRT5 knockdown,the protein levels of VCAM-1 and TF,as well as the mRNA levels of inflammatory factors including IL-6,IL-1β,VCAM-1,and E-selectin,were significantly upregulated(all P<0.001),whereas overexpression of SIRT5 reversed these effects.Transcriptome sequencing analysis indicated that SIRT5 regulated endothelial inflammation and coagulation responses by inhibiting the F2RL3/SERPINA3/TGF-β pathway.Conclusion·SIRT5 negatively regulates the F2RL3/SERPINA3/TGF-β signaling axis,thereby alleviating endothelial inflammation and promoting coagulation responses,suggesting its potential protective role in sepsis-induced lung injury.

Objective·To investigate the role and mechanism of sirtuin 5(SIRT5)in pulmonary microvascular endothelial cell injury in sepsis.Methods·Wild-type(WT)and Sirt5 gene knockout C57BL/6 male mice underwent cecal ligation and puncture(CLP)surgery.Following euthanasia,lung tissues were collected.Pulmonary inflammation was assessed using hematoxylin and eosin(H-E)staining;vascular leakage was evaluated by Evans blue(EB)staining;coagulation function in mice was analyzed via immunofluorescence staining of lung tissues.Immunohistochemical staining was employed to detect vascular cell adhesion molecule-1(VCAM-1)protein expression,thereby assessing endothelial inflammation in CLP-treated mice.By using gene editing technology,SIRT5 was knocked down or overexpressed in human umbilical vein endothelial cells(HUVECs),and the cells were subsequently stimulated with lipopolysaccharide(LPS)to induce endothelial inflammation.Protein expression levels of VCAM-1,tissue factor(TF),and other endothelial injury markers were detected by Western blotting,and inflammatory cytokines such as interleukin-6(IL-6)and IL-1β,were detected by quantitative real-time PCR(qPCR).In addition,transcriptomic sequencing was performed on HUVECs overexpressing SIRT5,and key genes including F2R-like thrombin or trypsin receptor 3(F2RL3),serpin family A member 3(SERPINA3),and transforming growth factor β2/β3(TGF-β2/3)were validated by qPCR.Results·Sirt5 knockout significantly aggravated lung injury in CLP mice,reducing their survival rates(P<0.001).H-E staining showed increased inflammatory infiltration in the lung tissue of the mice,while EB staining indicated increased vascular leakage(P<0.001).Immunofluorescence revealed elevated fibrinogen deposition.In HUVECs with SIRT5 knockdown,the protein levels of VCAM-1 and TF,as well as the mRNA levels of inflammatory factors including IL-6,IL-1β,VCAM-1,and E-selectin,were significantly upregulated(all P<0.001),whereas overexpression of SIRT5 reversed these effects.Transcriptome sequencing analysis indicated that SIRT5 regulated endothelial inflammation and coagulation responses by inhibiting the F2RL3/SERPINA3/TGF-β pathway.Conclusion·SIRT5 negatively regulates the F2RL3/SERPINA3/TGF-β signaling axis,thereby alleviating endothelial inflammation and promoting coagulation responses,suggesting its potential protective role in sepsis-induced lung injury.

[Purpose]To analyze and evaluate the application effect of quantitative fecal immuno-chemical test(FIT)in the opportunistic screening of colorectal cancer(CRC)in health examination population.[Methods]10 025 healthy individuals who completed quantitative FIT at the Health Management Cancer of Sichuan Cancer Hospital from January 1,2021 to December 31,2023 were included.Participants with positive FIT results were recommended for diagnostic colonoscopy.Quantitative FIT positivity rate,colonoscopy screening compliance rate,and colorectal lesion de-tection rate in the queue population were analyzed,the detection rate of colorectal lesions and colonoscopy resource load between quantitative FIT positive and negative colonoscopy screening groups at all levels were compared and the diagnostic efficacy of quantitative FIT for non progres-sive lesions and progressive lesions were explored.[Results]The positive rate of quantitative FIT was 6.24％(95％CI:5.77％～6.71％).The compliance rate of colonoscopy screening was 20.93％(95％CI:17.74％～24.12％).Among 284 colonoscopy patients,7 cases were detected with CRC,21 cases with advanced adenomas,52 cases with non advanced adenomas,40 cases with non adenomatous polyps,51 cases with other benign lesions,and 113 cases without abnormalities.The detection rates of non advanced adenomas,advanced adenomas,colorectal cancer,non pro-gressive lesions and progressive lesions in the quantitative FIT positive group were significantly higher than those in the quantitative FIT negative group.The detection rates of those without obvi-ous abnormalities were significantly lower than those in the quantitative FIT negative group,and the differences were statistically significant(all P＜0.05).The resource burden of colonoscopy in the quantitative FIT positive and negative groups was 5.46(95％CI:1.56～9.34)and 38.25(95％CI:30.55～45.95),respectively.The level of FIT measurement gradually increases with the severity of the lesion,and the difference between groups is statistically significant(H=48.308,P＜0.001).Quan-titative FIT has high sensitivity and negative predictive value for non progressive lesions and pro-gressive lesions,with values of 71.15％,85.71％and 90.20％,97.39％,respectively.The AUC values for quantitative FIT screening of non progressive lesions and progressive lesions were 0.653(95％CI:0.572～0.734,P=0.001)and 0.720(95％CI:0.631～0.808,P＜0.001),respectively.[Conclusion]Quantitative FIT,as a suitable technique for CRC opportunistic screening in health check-up population,has good diagnostic efficacy for non progressive lesions and progressive le-sions.Performing colonoscopy on FIT positive individuals can improve lesion detection rates while reducing colonoscopy resource consumption,aligning with China's healthcare resource landscape.

Objective:To analyze predictive risk indicators associated with the development of Kümmell's disease (KD) in patients with osteoporotic vertebral compression fractures (OVCFs).Methods:A 1∶1 frequency-matched case-control study design was employed, selecting patients who visited the Department of Spine Surgery at Liuzhou Workers' Hospital from January 2021 to June 2023. Patients were divided into case and control groups based on whether they progressed to Kümmell's disease (KD). Detailed demographic information, comorbidities, and laboratory data were collected, and baseline characteristics of the two groups were compared. Initial predictive variables significantly associated with the target variable were preliminarily screened through univariate analysis. A correlation heatmap was then constructed to assess collinearity among these variables, followed by further selection of potential predictors using the Lasso regression model. Finally, a multivariable logistic regression model was used for the prediction and analysis of KD-related risk indicators.Results:Univariate analysis identified significant predictors of Kümmell's disease, including patient age, bone mineral density, kyphotic Cobb angle, and multiple vertebral fractures. These were included in the subsequent Lasso regression analysis, which identified key predictors with non-zero coefficients: age, bone density, Cobb angle, multiple vertebral fractures, platelet count (PLT), aspartate aminotransferase/alanine aminotransferase (AST/ALT), albumin (Alb), albumin/globulin ratio (Alb/Glb), alkaline phosphatase (ALP), urea (UREA), serum uric acid (SUA), fibrinogen (Fn), blood glucose (BG), and C-reactive protein (CRP). The correlation heatmap revealed the correlation and collinearity risks between these variables, with ALT and AST/ALT showing a high correlation ( r=0.750) and PLT and Alb showing a low correlation ( r=-0.110). Multivariable logistic regression indicated that the presence of multiple vertebral fractures [ OR=2.078, 95% CI (1.072, 4.025), P=0.030], increased Cobb angle [ OR=1.033, 95% CI (1.008, 1.058), P=0.009], elevated levels of ALP [ OR=1.013, 95% CI(1.004, 1.023), P=0.006], and SUA [ OR=1.004, 95% CI (1.000, 1.007), P=0.043] were associated with an increased risk of KD in patients with OVCFs. Conversely, decreased levels of Fn [ OR=0.996, 95% CI (0.992, 0.999), P=0.008] were linked to an increased risk of KD. Conclusion:Multiple vertebral fractures, increased Cobb angle, elevated levels of ALP and SUA, along with decreased levels of Fn, can be used as early-warning indicators to predict whether patients with OVCFs will develop KD. Monitoring these indicators is crucial for the early detection and intervention in these patients.

Background and Aims:The Octoparms filter is a newly introduced domestically manufactured umbrella-shaped retrievable inferior vena cava (IVC) filter. A multicenter,parallel-controlled trial demonstrated its non-inferiority to the Celect filter. This study was performed to compare the clinical outcomes of the placement and retrieval of the Octoparms filter with those of the Denali filter to assess its safety and efficacy further.Methods:From May 2021 to May 2024,289 Denali filters (Denali group) and 78 Octoparms filters (Octoparms group) were placed and attempted to be retrieved at Beijing Shijitan Hospital,affiliated with Capital Medical University. After propensity score matching (PSM) of baseline characteristics,the incidence of filter tilt,wall apposition,vein wall penetration,retrieval success rates,and other relevant variables were compared between the two groups.Results:After PSM,77 patients were included in each group. Following matching,except for the significantly lower placement cost in the Octoparms group (P<0.05),all baseline characteristics (e.g.,gender,age,surgical indications,filter insertion route,IVC diameter,and angle) showed no statistically significant differences between the two groups (all P>0.05). The average indwelling time of the filter was longer in the Denali group compared to the Octoparms group (58 d vs. 47 d,P=0.004). There was no significant difference in the average filter tilt angle between the two groups (4.4° vs. 4.8°,P=0.71). While wall apposition or significant tilt was more frequent in the Octoparms group,the difference was not statistically significant (P>0.05). Both groups achieved a 100.0％ technical success rate for filter retrieval,with no complications such as filter fracture or vascular rupture during retrieval. Other retrieval-related variables (surgical approach,retrieval duration,retrieval techniques,and costs) also showed no significant differences between the two groups (all P>0.05).Conclusion:As a newly launched domestic filter,the Octoparms filter demonstrates comparable stability and retrieval rate to the Denali filter,and it is a safe and reliable choice.

Background and Aims:The Octoparms filter is a newly introduced domestically manufactured umbrella-shaped retrievable inferior vena cava (IVC) filter. A multicenter,parallel-controlled trial demonstrated its non-inferiority to the Celect filter. This study was performed to compare the clinical outcomes of the placement and retrieval of the Octoparms filter with those of the Denali filter to assess its safety and efficacy further.Methods:From May 2021 to May 2024,289 Denali filters (Denali group) and 78 Octoparms filters (Octoparms group) were placed and attempted to be retrieved at Beijing Shijitan Hospital,affiliated with Capital Medical University. After propensity score matching (PSM) of baseline characteristics,the incidence of filter tilt,wall apposition,vein wall penetration,retrieval success rates,and other relevant variables were compared between the two groups.Results:After PSM,77 patients were included in each group. Following matching,except for the significantly lower placement cost in the Octoparms group (P<0.05),all baseline characteristics (e.g.,gender,age,surgical indications,filter insertion route,IVC diameter,and angle) showed no statistically significant differences between the two groups (all P>0.05). The average indwelling time of the filter was longer in the Denali group compared to the Octoparms group (58 d vs. 47 d,P=0.004). There was no significant difference in the average filter tilt angle between the two groups (4.4° vs. 4.8°,P=0.71). While wall apposition or significant tilt was more frequent in the Octoparms group,the difference was not statistically significant (P>0.05). Both groups achieved a 100.0％ technical success rate for filter retrieval,with no complications such as filter fracture or vascular rupture during retrieval. Other retrieval-related variables (surgical approach,retrieval duration,retrieval techniques,and costs) also showed no significant differences between the two groups (all P>0.05).Conclusion:As a newly launched domestic filter,the Octoparms filter demonstrates comparable stability and retrieval rate to the Denali filter,and it is a safe and reliable choice.

Objective:To compare the efficacy of lower extremity three dimensional CT venography (CTV) and lower extremity ascending phlebography in evaluating recurrent varicose veins.Methods:A retrospective analysis was conducted on clinical data from 235 patients with unilateral recurrent varicose veins who were treated at the Department of Vascular Surgery,Beijing Shijitan Hospital,Capital Medical University, between January 2015 and December 2020.There were 112 males and 123 females, with an age of (62.5±11.4)years (range:24 to 75 years).Patients were stratified into two groups based on preoperative imaging examination:the CTV group (utilizing lower extremity venous ultrasound+lower extremity CTV) and the control group (employing lower extremity venous ultrasound+lower extremity ascending phlebography).The two groups were matched in a 1∶1 ratio using propensity score matching, resulting in 43 cases per group.Comparative analyses between the groups at the one-year postoperative follow-up were performed using independent sample t tests, Wilcoxon rank-sum tests, χ2 tests, and linear regression analysis. Results:One year post-surgery,the CTV group exhibited a lower venous clinical severity score (VCSS) compared to the control group( M(IQR),3.0(4.3) vs.4.0(5.8), Z=-2.038, P=0.040).Additionally, the chronic venous insufficiency patients′ quality of life questionnaire (CIVIQ-20) scores were significantly higher in the CTV group than in the control group (89.0(8.0) vs.82.5(17.0), Z=-2.627, P=0.010).Patients in the CTV group also experienced a shorter ulcer healing time compared to the control group (4.0(4.0) weeks vs.12.0(7.0) weeks, Z=-3.217, P<0.01).Both groups showed no clinically symptomatic recurrent varicose veins or ulcers.However, they exhibited ultrasound-detectable varicose vein recurrence, with no statistically significant difference ( χ2=0.453, P=0.500).The number of diseased vessels requiring management based on ultrasound supplemented by CTV was 16, while the number supplemented by ascending phlebography was 7,with a statistically significant difference ( χ2=4.800, P=0.030).Linear regression analysis demonstrated that clinical-etiology-anatomy-pathology clinical grading and the preoperative imaging examination method exerted independent influences on VCSS and CIVIQ-20 during the one-year postoperative assessment. Conclusions:CTV-assisted ultrasound enables a direct and comprehensive evaluation and localization of diseased veins in patients with recurrent varicose veins.The utilization of lower extremity vein ultrasound combined with CTV-guided management of lower extremity vessels in minimally invasive treatment significantly improves patient prognosis, surpassing the assessment provided by ascending phlebography.

OBJECTIVES: To investigate the role and mechanism of circRNA-SR-related CTD associated factor 8 (SCAF8) in regulating endothelial cell pyroptosis in high glucose environment. METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured and divided into six groups. The normal control group and high glucose control group were cultured in cell culture medium with 5 and 33 mmol/L glucose, respectively. The RNA control group, circRNA-SCAF8 inhibition group, miR-93-5p overexpression group and miR-93-5p inhibition group were added with non-functional siRNA, circRNA-SCAF8 inhibitor, miR-93-5p overexpression molecule and miR-93-5p inhibitor in high glucose environment, respectively. Cell viability and pyroptosis were detected by cell counting kit-8 (CCK-8) assay, flow cytometry and Hoechst 33342/propidium iodide fluorescence double staining. Western blotting and enzyme-linked immunosorbent assay were used to detect the expression of pyroptosis-related factors including apoptosis-associated speck-like protein containing a CARD (ASC), cysteine aspartic acid specific protease-1 (caspase-1) and Gasdermin D (GSDMD), NOD like receptor protein 3 (NLRP-3), thioredoxin interacting proteins (TXNIP), IL-18 and IL-1β. The expression of circRNA-SCAF8, miR-93-5p and TXNIP was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Fluorescence in situ hybridization (FISH) was used to locate circRNA-SCAF8 and miR-93-5p. Dual luciferase assay was used to verify the targeted regulatory relationship between miR-93-5p and upstream and downstream molecules. RESULTS: Compared with the RNA control group, the cell survival rate of circRNA-SCAF8 inhibition group and miR-93-5p overexpression group increased (both P<0.01), the pyroptosis decreased (both P<0.01), and the expressions of pyroptosis-related factors such as TXNIP, NLRP-3, caspase-1, GSDMD, ASC, IL-18 and IL-1β were significantly decreased (all P<0.05). The expression of miR-93-5p was significantly increased after inhibition of circRNA-SCAF8 (P<0.01), and the expression of circRNA-SCAF8 tended to decrease after overexpression of miR-93-5p, but with no statistical significance (P>0.05). Dual luciferase assay showed that miR-93-5p downre-gulated circRNA-SCAF8 expression by binding to the 3 ´ UTR region of circRNA-SCAF8, and miR-93-5p downregulated TXNIP expression by binding to the 3 ´ UTR region of TXNIP. FISH showed that circRNA-SCAF8 and miR-93-5p were both located in the cytoplasm and were highly associated in the cells. qRT-PCR showed that the relative expression of TXNIP increased or decreased after overexpression or inhibition of miR-93-5p compared with the RNA control group, respectively (both P<0.05), suggesting that miR-93-5p could regulate TXNIP gene expression. CONCLUSIONS CircRNA-SCAF8/miR-93-5p/TXNIP axis is involved in the regulation of pyroptosis in HUVECs under high glucose.
Humans ; Factor VIII ; RNA, Circular ; Endothelial Cells ; Interleukin-18 ; Pyroptosis ; In Situ Hybridization, Fluorescence ; Caspase 1 ; MicroRNAs/genetics* ; Carrier Proteins/genetics* ; RNA-Binding Proteins