Objective:To investigate the impact of blood pressure outcomes on the risk of arteriosclerosis in non-hypertensive populations.Methods:This study was a retrospective cohort study. All data were derived from Kailuan Cohort. Non-hypertensive individuals who completed two brachial-ankle pulse wave velocity (baPWV) measurements between January 2014 and December 2019 (using the first measurement as the baseline and the second as the follow-up) were enrolled, and clinical data such as blood pressure and baPWV were collected. According to the blood pressure level at baseline and follow-up, participants were divided into new-onset hypertension group (no hypertension at baseline but diagnosed at follow-up) and non-hypertension group (no hypertension at both baseline and follow-up). Multiple linear regression and multivariate logistic regression were used to analyze the impact of new-onset hypertension on arteriosclerosis progression. Subgroup analysis further classified participants into six blood pressure transition categories: normal-maintained, normal-to-high-normal, normal-to-hypertensive, high-normal-to-normal, high-normal-maintained, and high-normal-to-hypertensive groups. Multivariate logistic regression analysis was used to assess the impact of different blood pressure outcomes on arteriosclerosis progression.Results:A total of 7 049 participants were enrolled, with the age of (40.45±9.04) years, including 3 645 males (51.71%). There were 800 cases in the new-onset hypertension group and 6 249 individuals in the non-hypertension group. During follow-up, arteriosclerosis occurred in 2 154 cases (30.56%). Multivariable linear regression analysis revealed a positive correlation between new-onset hypertension and baPWV levels. The baPWV in the new-onset hypertension group was significantly higher by 63.94 cm/s compared to the non-hypertension group ( β=63.94, P<0.01). Additionally, the risk of arteriosclerosis in the new-onset hypertension group was 2.09 times that of the non-hypertension group ( OR=2.09, 95% CI: 1.77-2.46, P<0.01). Subgroup analysis revealed significantly higher arteriosclerosis risks in normal-to-high-normal ( OR=1.65, 95% CI 1.38-1.98, P<0.01), normal-to-hypertensive ( OR=2.47, 95% CI 1.70-3.59, P<0.01), high-normal-maintained ( OR=1.50, 95% CI 1.21-1.86, P<0.01), and high-normal-to-hypertensive groups ( OR=2.86, 95% CI 2.20-3.73, P<0.01) than normal-maintained group, except for a non-significant difference in high-normal-to-normal group ( OR=0.95, 95% CI 0.74-1.20, P>0.05). Conclusion:Blood pressure outcome in non-hypertensive populations is closely related to arteriosclerosis risk. Progression to or maintenance of high-normal blood pressure or higher levels substantially increases arteriosclerosis risk, while regression from high-normal to normal blood pressure shows no significant increase in arteriosclerosis risk.

Objective:To investigate the impact of blood pressure outcomes on the risk of arteriosclerosis in non-hypertensive populations.Methods:This study was a retrospective cohort study. All data were derived from Kailuan Cohort. Non-hypertensive individuals who completed two brachial-ankle pulse wave velocity (baPWV) measurements between January 2014 and December 2019 (using the first measurement as the baseline and the second as the follow-up) were enrolled, and clinical data such as blood pressure and baPWV were collected. According to the blood pressure level at baseline and follow-up, participants were divided into new-onset hypertension group (no hypertension at baseline but diagnosed at follow-up) and non-hypertension group (no hypertension at both baseline and follow-up). Multiple linear regression and multivariate logistic regression were used to analyze the impact of new-onset hypertension on arteriosclerosis progression. Subgroup analysis further classified participants into six blood pressure transition categories: normal-maintained, normal-to-high-normal, normal-to-hypertensive, high-normal-to-normal, high-normal-maintained, and high-normal-to-hypertensive groups. Multivariate logistic regression analysis was used to assess the impact of different blood pressure outcomes on arteriosclerosis progression.Results:A total of 7 049 participants were enrolled, with the age of (40.45±9.04) years, including 3 645 males (51.71%). There were 800 cases in the new-onset hypertension group and 6 249 individuals in the non-hypertension group. During follow-up, arteriosclerosis occurred in 2 154 cases (30.56%). Multivariable linear regression analysis revealed a positive correlation between new-onset hypertension and baPWV levels. The baPWV in the new-onset hypertension group was significantly higher by 63.94 cm/s compared to the non-hypertension group ( β=63.94, P<0.01). Additionally, the risk of arteriosclerosis in the new-onset hypertension group was 2.09 times that of the non-hypertension group ( OR=2.09, 95% CI: 1.77-2.46, P<0.01). Subgroup analysis revealed significantly higher arteriosclerosis risks in normal-to-high-normal ( OR=1.65, 95% CI 1.38-1.98, P<0.01), normal-to-hypertensive ( OR=2.47, 95% CI 1.70-3.59, P<0.01), high-normal-maintained ( OR=1.50, 95% CI 1.21-1.86, P<0.01), and high-normal-to-hypertensive groups ( OR=2.86, 95% CI 2.20-3.73, P<0.01) than normal-maintained group, except for a non-significant difference in high-normal-to-normal group ( OR=0.95, 95% CI 0.74-1.20, P>0.05). Conclusion:Blood pressure outcome in non-hypertensive populations is closely related to arteriosclerosis risk. Progression to or maintenance of high-normal blood pressure or higher levels substantially increases arteriosclerosis risk, while regression from high-normal to normal blood pressure shows no significant increase in arteriosclerosis risk.

Background and aims:Antiviral therapy is essential for hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF).No data are available on the long-term prognosis or safety of tenofovir alafenamide(TAF),tenofovir disoproxil fumarate(TDF),or entecavir(ETV)in treating HBV-ACLF globally.This study was conducted to investigate the long-term efficacy and safety of the three nucleos(t)ide analogs in the treatment of HBV-ACLF.Methods:In this prospective,real-world cohort study,patients with HBV-ACLF were assigned to the TAF,TDF,and ETV groups.A total of 199 patients completed the 144-week follow-up.After propensity score matching(PSM),44 patients remained in each group for further analysis of survival status,incidence of hepatocellular carcinoma(HCC),virological response,and liver and renal function indicators.Results:In the original cohort,HCC developed in one patient in each group.No serious drug-related adverse events were observed.In the PSM cohort,the 144-week survival rates were 56.82％,75.00％,and 59.09％in the TAF,TDF,and ETV groups,respectively(P=0.118).When stratified into noncirrhosis and cirrhosis subgroups at baseline,the survival rate of the ETV group was slightly lower than that of the TAF and TDF group in noncirrhosis patients(P=0.338),and the survival rate of the TAF group was slightly lower than that of the TDF and ETV group in cirrhosis patients(P=0.052),but the differences were not statistically significant.The long-term overall survival rates in the TAF,TDF,and ETV groups were comparable.After 144 weeks,no significant difference in the virological response rate or liver or renal function indicators was found among the three groups,except for the level of aspartate amino-transferase,which was significantly higher in the TDF group than in the ETV group at week 144(P=0.001).Conclusions:There were no significant differences in the survival rate,incidence of HCC,efficacy or safety associated with the use of these three nucleos(t)ide analogs in treating HBV-ACLF.Trial registration:ClinicalTrials.gov NCT03920618.

Objective To synthesize a Salphen-based Fe-N2O2@C material with high peroxidase(POD)-mimicking activity and sonosensitivity for the synergistic sonodynamic(SDT)and chemodynamic(CDT)therapy of tumors.Methods Fe-N2O2 was synthesized via the hydrothermal method,and Fe-N2O2@C was prepared by incorporating a ketjen black substrate.The morphology,structure,composition,enzyme mimic activity for reactive oxygen species(ROS)production,and sonosensitivity of the material were characterized.The ability and mechanism of Fe-N2O2@C to perform synergistic SDT and CDT killing of 4T1 mouse breast cancer cells were explored through in vitro experiments.The in vivo tumor-killing ability of Fe-N2O2@C combined with ultrasound irradiation was investigated using a subcutaneous 4T1 tumor-bearing mouse model.Results FFe-N2O2 and Fe-N2O2@C were both irregularly shaped nanospheres with average particle sizes of 25.9 nm and 36.2 nm,respectively.XRD,FTIR,and XPS analyses confirmed that both Fe-N2O2 and Fe-N2O2@C possessed a Salphen covalent organic framework structure with M-N2O2 coordination,and the ketjen black loading had no significant impact on this structure.Compared to Fe-N2O2,Fe-N2O2@C exhibited high POD-mimicking activity(with Km reduced from 19.32 to 5.82 mmol/L and vmax increased from 2.51×10-8 to 8.92×10-8 mol/[L·s])and sonosensitivity.Fe-N2O2@C in combination with ultrasound irradiation could produce a large amount of ROS within cells and a subsequent significant decrease in mitochondrial membrane potential,thereby inducing TEM-observable mitochondrial damage and causing cell apoptosis and death.In addition,in vivo experiments showed that Fe-N2O2@C in combination with ultrasound irradiation could effectively inhibit tumor growth in a 4T1 subcutaneous tumor-bearing mouse model without significant in vivo toxicity.Conclusion In this study,we prepared a Salphen-based Fe-N2O2@C material with good biocompatibility,which can be used in combination with ultrasound irradiation to achieve SDT and CDT synergistic killing of tumor cells and inhibit tumor growth.This Salphen-based Fe-N2O2@C nanomaterial shows promising potential for multimodal tumor therapy.

Objective:To provide evidence for optimizing the screening strategy for gastric cancer (GC), we evaluated the risk of incident GC for individuals with different precancerous gastric lesions in a prospective cohort study.Methods:Based on the National Upper Gastrointestinal Cancer Early Detection Program launched in Linqu, Shandong, a high-risk area of gastric cancer in China, we included a total of 14 087 subjects diagnosed with different gastric lesions stages by endoscopic screening from 2012 to 2018. Study subjects were prospectively followed up until December 31, 2019. The incidence of GC during the follow-up was ascertained by repeated endoscopic examinations, cancer, death registry reports, and active follow-up of study subjects and was confirmed by reviewing medical records extracted from the hospital information management system. The Poisson regression model was applied to calculate the relative risk ( RR) and 95% CI for GC occurrence among subjects with different gastric lesions. Results:Among 14 087 subjects with different gastric lesions as determined by their first endoscopic examination in 2012-2018, 7 608 (54.00%) had a global diagnosis of superficial gastritis (SG), 2 848 (20.22%) had chronic atrophic gastritis (CAG), 3 103 (22.03%) had intestinal metaplasia (IM), and 520 (3.69%) had low-grade intestinal neoplasia (LGIN). During the follow-up, 109 subjects were diagnosed with GC, including 63 with high-grade intestinal neoplasia (HGIN) and 46 with invasive GC. Compared to subjects having normal gastric mucosa or SG, those with CAG ( RR=3.85, 95% CI: 2.04-7.28), IM ( RR=5.18, 95% CI: 2.79-9.60), and LGIN ( RR=19.08, 95% CI: 9.97-36.53) had significantly increased risk of progression to GC. Individuals with these gastric lesions had an elevated risk of developing HGIN and invasive GC. For subjects with LGIN, the RR was 22.96 (95% CI: 9.71-54.27) for developing HGIN and 14.64 (95% CI: 5.37-39.93) for developing invasive GC. Subgroup analyses found that all age group subjects with LGIN diagnosed during the initial endoscopic examination had a significantly increased risk of developing the GC. Conclusions:Our large-scale prospective study on a high-risk area of GC showed that most residents aged 40-69 years had gastric lesions of different stages. Subjects with more advanced gastric lesions had a significantly increased risk of progression to GC.

Objective To improve the quality standards of Kunxian capsules (KC) and effectively control the product quality. Methods Triptolide, icariin and hypericin were used as the indicator components, to increase or improve the thin layer chromatography (TLC) identification methods of Kunming begonia, epimedium and dodder. Agilent ZORBA SB-C₁₈ (4.6 mm×250 mm, 5 μm) as a chromatographic column, the HPLC method for the determination of triptolide was improved with acetonitrile-0.1% formic acid solution as the mobile phase and 220 nm as the detection wavelength. Results The spots in the TLC method of Kunming begonia, epimedium and dodder has strong specificity, good and clear separation of characteristic spots, negative and no interference. The quantitative analysis of the content of triptolide in KC showed that there is a good linear relationship (r=0.9995) between the mass concentration of triptolide and the peak area in the range of 40.16-502.00 μg/ml, the average recovery was 98.12%, RSD was 8.25%, and the accuracy was good. Conclusion The TLC identification method and HPLC method established in this experiment have strong specificity and good reproducibility, and can effectively control the quality of KC.

Traditional survival methods have a wide application in the field of biomedical research. However, applying traditional survival methods requires data to meet a set of special assumptions while the Random Survival Forest model can overcome this inconvenience. Herein, we used the clinical data of Primary Biliary Cholangitis (PBC) from Mayo Clinic to introduce and demonstrate Random Survival Forest model from mathematical principles, model building, practical example and attentions, aiming to provide a novel method for doing survival analysis.

The liquid chromatography tandem mass spectrometry was used to detect the urinary proteomics of 223 residents aged 40-69 years old who participated in the National Upper Gastrointestinal Cancer Early Detection Program in Linqu County, Shandong Province from November 22 to December 7, 2018, and analyze the alcohol consumption related proteomic profiles and individual urinary protein. There were significant differences in urinary protein profiles between alcohol consumption group and non-alcohol consumption group. The expression of 26 urinary proteins was up-regulated and 20 urinary proteins were down-regulated in alcohol consumption group ( P<0.05). The differentially expressed proteins had enzyme inhibitor activity and phospholipid binding function, and mainly enriched in pathways involving proximal tubule bicarbonate regeneration, complement and coagulation cascade, and cholesterol metabolism. The protein expressions of complement factor I (CFI), angiotensin converting enzyme 2 (ACE2) and protein C inhibitor (SERPINA5) were positively correlated with daily alcohol consumption.

Traditional survival methods have a wide application in the field of biomedical research. However, applying traditional survival methods requires data to meet a set of special assumptions while the Random Survival Forest model can overcome this inconvenience. Herein, we used the clinical data of Primary Biliary Cholangitis (PBC) from Mayo Clinic to introduce and demonstrate Random Survival Forest model from mathematical principles, model building, practical example and attentions, aiming to provide a novel method for doing survival analysis.

The liquid chromatography tandem mass spectrometry was used to detect the urinary proteomics of 223 residents aged 40-69 years old who participated in the National Upper Gastrointestinal Cancer Early Detection Program in Linqu County, Shandong Province from November 22 to December 7, 2018, and analyze the alcohol consumption related proteomic profiles and individual urinary protein. There were significant differences in urinary protein profiles between alcohol consumption group and non-alcohol consumption group. The expression of 26 urinary proteins was up-regulated and 20 urinary proteins were down-regulated in alcohol consumption group ( P<0.05). The differentially expressed proteins had enzyme inhibitor activity and phospholipid binding function, and mainly enriched in pathways involving proximal tubule bicarbonate regeneration, complement and coagulation cascade, and cholesterol metabolism. The protein expressions of complement factor I (CFI), angiotensin converting enzyme 2 (ACE2) and protein C inhibitor (SERPINA5) were positively correlated with daily alcohol consumption.