OBJECTIVE To observe the intervention effect of puerarin on the rats with bacterial periodontitis by reg-ulating nucleotide-binding oligomeric domain-like receptor protein 3/Caspase-1(NLRP3/Caspase-1)signaling pathways.METHODS Totally 44 male SPF rats were chosen as subjects and were divided into the blank group,the model group,the puerarin group and the puerarin plus inhibitor group.The models of rats with bacterial periodon-titis were successfully established.The periodontal indexes and alveolar resorption were observed and compared a-mong the groups.RESULTS The sulcus bleeding index(SBI)and plaque index(PLI)scores of the model group and the puerarin plus inhibitor group were higher than those of the blank group;the NLRP3 level was 0.87±0.09 in the model group,0.85±0.08 in the puerarin plus inhibitor group,higher than 0.18±0.03 in the blank group;the Caspase-1 level was 1.15±0.11 in the model group,1.03±0.10 in the puerarin plus inhibitor group,higher than 0.35±0.04 in the blank group.The trabecular separation spacing(Tb.Sp),cemento-enamel junction-facial bone crest(CEJ-FBC),interleukin--1β(IL-1β)level,interleukin-6(IL-6)level,tumor necrosis factor-α(TNF-α)level and osteoclast counts of the model group and the puerarin plus inhibitor group were higher than those of the blank group;while the trabecular thickness(Tb.Th),bone volume/tissue volume(BV/TV)and bone mineral density(BMD)of the model group and the puerarin plus inhibitor group were lower than those of the blank group.The SBI and PLI scores of the puerarin group were lower than those of the model group;the NLRP3 level of the puerarin group was 0.20±0.04,lower than 0.87±0.09 of the model group;the Caspase-1 level of the puerarin group was 0.37±0.05,lower than 1.15±0.11 of the model group.The Tb.Sp,CEJ-FBC,IL-1βlevel,IL-6 lev-el,TNF-α level and osteoclast counts of the puerarin group were lower than those of the model group;while the Tb.Th,V/V and BMD of the puerarin group were higher than those of the model group.The SBI and PLI score of the puerarin plus inhibitor group were higher than those of the puerarin group;the NLRP3 level of the puerarin plus inhibitor group was 0.85±0.08,higher than 0.20±0.04 of the puerarin group;the Caspase-1 level of the pu-erarin plus inhibitor group was 1.03±0.10,higher than 0.37±0.05 of the puerarin group.The Tb.Sp,CEJ-FBC,IL-1β level,IL-6 level,TNF-α level and osteoclast counts of the puerarin plus inhibitor group were higher than those of the puerarin group,while the Tb.Th,V/V and BMD of the puerarin plus inhibitor group were low-er than those of the puerarin group,there were significant differences in the above comparisons(P＜0.05).CONCLUSIONS Puerarin can effectively reduce the periodontal plaque index and bleeding index of the rats with bacterial,reduce the levels of inflammatory factors and alleviate the damage of tissue.The action mechanisms may be associated with the NLRP3/Caspase-1 signaling pathways.

Objective:To investigate the value of coronary CTA (CCTA)-based traditional features and radiomics of plaque in the identification of culprit lesions that caused acute myocardial infarction (AMI).Methods:This was a retrospective multicenter study. From July 2016 to November 2023, a total of 344 patients from the Affiliated Hospital of Qingdao University (training cohort, n=184), Shandong Provincial Hospital Affiliated to Shandong First Medical University (validation cohort, n=88) and Qilu Hospital of Shandong University (test cohort, n=72) who received percutaneous coronary intervention (PCI) due to AMI and underwent CCTA within 48 hours of AMI were enrolled. The culprit plaques and non-culprit plaques were identified using a combination of electrocardiogram, CCTA, and angiographic findings. The vessel, plaque location, plaque type, Coronary Artery Disease-Reporting and Data System (CAD-RADS) score, high-risk plaque characteristics, plaque length, plaque volume, and burden were analyzed, and 1 904 radiomics features were extracted for each plaque. The traditional imaging model, the radiomics model, and the combined model were established by using multivariate Logistic regression analysis. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of each model in identifying culprit lesions. The DeLong test was used for the comparison of AUC between every two models. The net reclassification index (NRI) was used to evaluate the incremental value of the combined model to the traditional imaging model and the radiomics model. The decision curve analysis (DCA) was used to assess the clinical net benefit of these models. A correlation heatmap was used to evaluate the correlation between the radiomics score and traditional CCTA factors. The interpretable analysis of the decision process of the combined model was performed by the Shapley Additive exPlanations (SHAP). Results:In the validation cohort and the test cohort, the AUC of the traditional imaging model developed by the vessel, plaque type, positive remodeling and CAD-RADS score was 0.898 (95% CI 0.869-0.922) and 0.881 (95% CI 0.848-0.910), respectively. The radiomics model developed by six radiomics features was 0.863 (95% CI 0.831-0.891) and 0.863 (95% CI 0.827-0.864), respectively. The AUC of the combined model was 0.930 (95% CI 0.905-0.950)and 0.919 (95% CI 0.889-0.942), respectively. In the validation cohort and the test cohort, the AUC of the combined model was higher than that of the traditional imaging model ( Z=4.013, 4.272, P<0.001) and that of the radiomics model ( Z=4.819, 3.784, P<0.001), respectively. In the validation cohort, the combined model yielded an NRI of 20.43% (95% CI 10.43%-30.44%, P<0.001) and 20.21% (95% CI 9.62%-30.80%, P<0.001) for identifying culprit lesions compared with the traditional imaging model and the radiomics model, respectively. In the test cohort, the combined model yielded an NRI of 28.05% (95% CI 16.72%-39.38%, P<0.001) and 23.57% (95% CI 13.58%-33.56%, P<0.001) for identifying culprit lesions compared with the traditional imaging model and the radiomics model, respectively. DCA showed the combined model had the highest clinical net benefit. The correlation heatmap showed the radiomics score was not correlated or only weakly correlated with traditional CCTA factors. SHAP indicated the radiomics and CAD-RADS score contributed significantly to the model. Conclusion:The CCTA-based traditional features and radiomics of plaque have favorable performance for the identification of culprit plaques in patients with AMI.

Objective:To analyze the current status of the standard system construction for smart health and elderly care in China,analyze the framework of the standard system,and propose policy recommendations for the construction of the standard system.Methods:The standard system of smart health and elderly care were searched on the websites of the State Council of China,the National Standard Information Public Service Platform,and the sub-websites of national,industry,local,group,and enterprise standards.Policy text analysis was used to explore the current status and framework of standard system construction.Results:Currently,67 standards related to smart health and elderly care in China were included,including 0 national standards,2 industry standard,10 local standards,31 group standards,and 24 enterprise standards.These standards formed a subsystem that covered general,data,product,platform,and service standards.Conclusion:The construction of the standard system of smart health and elderly care in China has achieved certain results,but there are still shortcomings,and it is necessary to strengthen the top-level design and build a perfect framework of the standard system.

OBJECTIVE To observe the intervention effect of puerarin on the rats with bacterial periodontitis by reg-ulating nucleotide-binding oligomeric domain-like receptor protein 3/Caspase-1(NLRP3/Caspase-1)signaling pathways.METHODS Totally 44 male SPF rats were chosen as subjects and were divided into the blank group,the model group,the puerarin group and the puerarin plus inhibitor group.The models of rats with bacterial periodon-titis were successfully established.The periodontal indexes and alveolar resorption were observed and compared a-mong the groups.RESULTS The sulcus bleeding index(SBI)and plaque index(PLI)scores of the model group and the puerarin plus inhibitor group were higher than those of the blank group;the NLRP3 level was 0.87±0.09 in the model group,0.85±0.08 in the puerarin plus inhibitor group,higher than 0.18±0.03 in the blank group;the Caspase-1 level was 1.15±0.11 in the model group,1.03±0.10 in the puerarin plus inhibitor group,higher than 0.35±0.04 in the blank group.The trabecular separation spacing(Tb.Sp),cemento-enamel junction-facial bone crest(CEJ-FBC),interleukin--1β(IL-1β)level,interleukin-6(IL-6)level,tumor necrosis factor-α(TNF-α)level and osteoclast counts of the model group and the puerarin plus inhibitor group were higher than those of the blank group;while the trabecular thickness(Tb.Th),bone volume/tissue volume(BV/TV)and bone mineral density(BMD)of the model group and the puerarin plus inhibitor group were lower than those of the blank group.The SBI and PLI scores of the puerarin group were lower than those of the model group;the NLRP3 level of the puerarin group was 0.20±0.04,lower than 0.87±0.09 of the model group;the Caspase-1 level of the puerarin group was 0.37±0.05,lower than 1.15±0.11 of the model group.The Tb.Sp,CEJ-FBC,IL-1βlevel,IL-6 lev-el,TNF-α level and osteoclast counts of the puerarin group were lower than those of the model group;while the Tb.Th,V/V and BMD of the puerarin group were higher than those of the model group.The SBI and PLI score of the puerarin plus inhibitor group were higher than those of the puerarin group;the NLRP3 level of the puerarin plus inhibitor group was 0.85±0.08,higher than 0.20±0.04 of the puerarin group;the Caspase-1 level of the pu-erarin plus inhibitor group was 1.03±0.10,higher than 0.37±0.05 of the puerarin group.The Tb.Sp,CEJ-FBC,IL-1β level,IL-6 level,TNF-α level and osteoclast counts of the puerarin plus inhibitor group were higher than those of the puerarin group,while the Tb.Th,V/V and BMD of the puerarin plus inhibitor group were low-er than those of the puerarin group,there were significant differences in the above comparisons(P＜0.05).CONCLUSIONS Puerarin can effectively reduce the periodontal plaque index and bleeding index of the rats with bacterial,reduce the levels of inflammatory factors and alleviate the damage of tissue.The action mechanisms may be associated with the NLRP3/Caspase-1 signaling pathways.

In recent years,protein and polypeptide drugs have developed rapidly and have been widely used to treat cancer,hepatitis,and other diseases.The activity of proteins and polypeptides is closely related to their structure.Protein structures can be divided into four levels:primary,secondary,tertiary,and quaternary structures.The primary structure determines the advanced structure and biological functions of proteins.To ensure drug safety,it is necessary to carry out structural characterization and quality control.The advanced structure is the basis for proteins to express their functions and activities,and changes in spatial structure can lead to alterations in functions.This article reviews the progress of research on the primary and advanced structure characterization of proteins and polypeptides,including techniques such as reversed-phase high-performance liquid chromatography,Edman degradation,mass spectrometry,and spectroscopy.It aims to provide a reference for the structural characterization and quality control of other protein and polypeptide drug products.

In recent years,protein and polypeptide drugs have developed rapidly and have been widely used to treat cancer,hepatitis,and other diseases.The activity of proteins and polypeptides is closely related to their structure.Protein structures can be divided into four levels:primary,secondary,tertiary,and quaternary structures.The primary structure determines the advanced structure and biological functions of proteins.To ensure drug safety,it is necessary to carry out structural characterization and quality control.The advanced structure is the basis for proteins to express their functions and activities,and changes in spatial structure can lead to alterations in functions.This article reviews the progress of research on the primary and advanced structure characterization of proteins and polypeptides,including techniques such as reversed-phase high-performance liquid chromatography,Edman degradation,mass spectrometry,and spectroscopy.It aims to provide a reference for the structural characterization and quality control of other protein and polypeptide drug products.

Objectives:To systematically evaluate the effectiveness and safety of sacubitril valsartan in the treatment of heart failure with mildly reduced ejection fraction(HFmrEF).Methods:Computer searches were conducted on PubMed,Embase,China National Knowledge Infrastructure(CNKI),VIP,and Wanfang Data,all from the time of database establishment until December 31,2023.Randomized controlled trials(RCT)of sacubitril valsartan(experimental group)compared to conventional drugs such as renin angiotensin converting enzyme inhibitors/angiotensin Ⅱ receptor antagonists(control group)for the treatment of HFmrEF were collected.After screening literature and extracting data,meta-analysis was conducted using Stata 15.0 and Rev Man 5.3 software,and bias and sensitivity analyses were published in parallel.Results:A total of 13 RCTs were included,with a total of 1 150 patients.The meta-analysis results showed that all-cause mortality risk of patients(RR=0.63,95%CI:0.45-0.86,P=0.004),and the risk of elevated blood creatinine(RR=0.65,95%CI:0.50-0.84,P=0.001)in the experimental group were significantly lower than those in the control group.The level of six-minute walk test post therapy was significantly higher in the experimental group patients than that in the control group(weighted mean differences[WMD]=66.33 m,95%CI:11.77-120.90,P=0.02).There was no statistically significant difference in the comparison on the readmission rate of heart failure(RR=0.87,95%CI:0.61-1.24,P=0.43),NT-proBNP levels(WMD=319.67 pg/ml,95%CI:-823.36 to 1 462.70,P=0.58),soluble suppression of tumorigenicity 2(sST2)levels(WMD=4.48 μg/L,95%CI:-0.58 to 9.54,P=0.08),incidence of hypotension(RR=1.03,95%CI:0.61-1.76,P=0.90),and incidence of hyperkalemia(RR=0.95,95%CI:0.67-1.33,P=0.75)between the two groups of patients after treatment.The results of publication bias and sensitivity analysis both indicated a high possibility of publication bias,and some indicators had unstable results.Conclusions:Sacubitril valsartan may effectively reduce all-cause mortality,and the risk of elevated blood creatinine in HFmrEF patients,improving their long-term prognosis.However,the incidence of hypotension and hyperkalemia remains unclear.

Objectives:To systematically evaluate the effectiveness and safety of sacubitril valsartan in the treatment of heart failure with mildly reduced ejection fraction(HFmrEF).Methods:Computer searches were conducted on PubMed,Embase,China National Knowledge Infrastructure(CNKI),VIP,and Wanfang Data,all from the time of database establishment until December 31,2023.Randomized controlled trials(RCT)of sacubitril valsartan(experimental group)compared to conventional drugs such as renin angiotensin converting enzyme inhibitors/angiotensin Ⅱ receptor antagonists(control group)for the treatment of HFmrEF were collected.After screening literature and extracting data,meta-analysis was conducted using Stata 15.0 and Rev Man 5.3 software,and bias and sensitivity analyses were published in parallel.Results:A total of 13 RCTs were included,with a total of 1 150 patients.The meta-analysis results showed that all-cause mortality risk of patients(RR=0.63,95%CI:0.45-0.86,P=0.004),and the risk of elevated blood creatinine(RR=0.65,95%CI:0.50-0.84,P=0.001)in the experimental group were significantly lower than those in the control group.The level of six-minute walk test post therapy was significantly higher in the experimental group patients than that in the control group(weighted mean differences[WMD]=66.33 m,95%CI:11.77-120.90,P=0.02).There was no statistically significant difference in the comparison on the readmission rate of heart failure(RR=0.87,95%CI:0.61-1.24,P=0.43),NT-proBNP levels(WMD=319.67 pg/ml,95%CI:-823.36 to 1 462.70,P=0.58),soluble suppression of tumorigenicity 2(sST2)levels(WMD=4.48 μg/L,95%CI:-0.58 to 9.54,P=0.08),incidence of hypotension(RR=1.03,95%CI:0.61-1.76,P=0.90),and incidence of hyperkalemia(RR=0.95,95%CI:0.67-1.33,P=0.75)between the two groups of patients after treatment.The results of publication bias and sensitivity analysis both indicated a high possibility of publication bias,and some indicators had unstable results.Conclusions:Sacubitril valsartan may effectively reduce all-cause mortality,and the risk of elevated blood creatinine in HFmrEF patients,improving their long-term prognosis.However,the incidence of hypotension and hyperkalemia remains unclear.

Objective To develop an endothelialized microfluidic chip model that simulates the spatial architecture and bioactivity of retinal vasculature,enabling thrombosis modeling and thrombolytic efficacy validation.Methods A tri-level microvascular network chip(300/200/100 μm diameters)with bifurcated architecture was fabricated using soft lithography.Human retinal microvascular endothelial cells(HRMECs)were perfused into channels,with endothelial coverage monitored via phase-contrast microscopy and F-actin staining.Cellular bioactivity was assessed using mitochondrial membrane potential probes(5,5,6,6-Tetrachloro-1,1,3,3-tetraethylbenzimidazolylcarbocyanine iodide,JC-1)and nitric oxide(NO)quantification.Fresh blood samples from 10 healthy donors(Yongchuan Hospital Affiliated to Chongqing Medical University,March to June 2024)were perfused with digital injection pump to mimic blood flow in human body into 3 experimental groups:normal whole blood,and TNF-α-activated endothelium+normal blood,TNF-α-activated endothelium+TNF-α-treated blood.Three inlet blood flow rates of 37.8、11.1 and 3.5 μL/min were set in each group.Two experimental groups,normal saline and recombinant human tissue-type plasminogen activator(rtPA),were established using the endothelialized microfluidic thrombosis model to validate thrombolytic efficacy.Endothelial functional impacts were assessed through integrated DAPI/NO staining and thrombosis model analysis across 3 intervention phases:pre-thrombosis,post-thrombosis,and post-thrombolysis.Results A tri-level microfluidic vascular model(300/200/100 μm diameters)was successfully constructed.In 72 h after endothelial cell perfusion,complete channel coverage was achieved,with phase-contrast microscopy and F-actin staining confirming confluent cellular alignment.JC-1/NO assays validated preserved endothelial bioactivity.Compared with the whole blood group,both TNF-α-activated endothelium+normal blood and TNF-α-activated endothelium+TNF-α-treated blood groups exhibited significantly increased thrombus occupancy rates at identical flow rates(all P<0.001).Notably,TNF-α-activated endothelium+TNF-α-treated blood group demonstrated the highest thrombus ratio at 3.5 μL/min(P<0.001).The rtPA group showed superior thrombolytic efficacy versus saline(P<0.001).Endothelial monolayer integrity was maintained across intervention phases,with thrombosis triggering significant NO elevation(P<0.001).Conclusion Our retinal vasculature-mimetic microfluidic model enables precise thrombosis modeling and drug evaluation,providing new methodology for studying retinal vascular occlusive diseases.

Objective:To analyze the efficacy and safety of splenic artery occlusion combined with microwave ablation (MWA) in the treatment of hepatocellular carcinoma (HCC) complicated with liver cirrhosis and hypersplenism.Methods:Clinical data of 24 patients with HCC complicated with cirrhosis and secondary hypersplenism admitted to Airport Hospital of Tianjin Cancer Hospital from August 2023 to May 2024 were retrospectively analyzed, including 13 males and 11 females, aged (57.4±7.8) years. All patients were treated with splenic artery occlusion combined with MWA of spleen. Spleen volume measured by MRI before and after MWA, blood routine changes and postoperative complications (fever, bleeding, pain, renal failure and thrombosis) were analyzed.Results:The splenic volume of 24 patients measured by MRI before MWA was 692.4 (504.7, 1023.7) cm 3, and decreased to 225.0 (186.4, 285.6) cm 3 after treatment for 60 days ( Z=-3.23, P=0.001). The red blood cell counts were comparable before and after microwave ablation. The white blood cell count before MWA was 4.3 (3.2, 5.3)×10 9/L, which increased to 11.0 (8.6, 15.8)×10 9/L three days after treatment, and to 5.0 (3.3, 6.1)×10 9/L 90 days after treatment ( Z=-4.70, -0.34, P<0.001, P=0.732). The platelet count of the patients was 47.0 (39.0, 67.0)×10 9/L before MWA, which increased to 155.0 (120.3, 214.3)×10 9/L seven days after Treatment, and to 77.0 (63.0, 125.0)×10 9/L 90 days after treatment ( Z=-5.29, -2.51, P<0.001, P=0.012). None of the patients had obvious bleeding and no death occured. One patient (4.2%) developed renal failure, one patient (4.2%) had splenic venous thrombosis, 4 patients (16.7%) had pain of different degrees, and 5 patients (20.8%) had low fever. Conclusion:Splenic artery occlusion combined with MWA in the treatment of HCC complicated with liver cirrhosis and hypersplenism can significantly reduce spleen volume and increase platelet level with acceptable complications.