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 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.

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.

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.

Objective: To analyze the association between circular RNAs expression in serum and gastric cancer and evaluate the potential of the related markers in early diagnosis of gastric cancer. Methods: Forty eight gastric cancer cases in Linqu County People’s Hospital were selected as case group, and 48 controls matched by age and sex were randomly selected in the gastric cancer screening cohort during the same period. The expression levels of hsa_circ_002059, hsa_circ_0000096 and hsa_circ_0001895 were detected by quantitative real-time PCR. The results were compared between case group and control group. Results: The positive expression rates of hsa_circ_002059, hsa_circ_0000096 and hsa_circ_0001895 were 70.8%, 47.9%, 75.0% in case group, slightly higher than those in control group (58.3%, 31.3%, 60.4%), although P values were all more than 0.05. The expression level medians of the 3 candidate circRNAs expression levels were 1.60% (0-5.64%), 0 (0-0.61%), 0.91% (0.06%-1.88%) in case group, while 0.05% (0-6.07%), 0 (0-0.34%), 0.42% (0-1.39%) in control group, respectively. Conditional logistic regression analysis showed that the association strength of high expressions of 3 candidate circRNAs with gastric cancer showed an increase trend, but the differences had no significance after adjusted by Helicobacter pylori infection, smoking and drinking status (all P>0.05). Further analysis by combining the 3 candidate circRNAs showed the increased strength of association between circRNAs and gastric cancer with the elevated number of positive circRNAs in serum (trend test P=0.040) compared with circRNAs negative persons. Conclusion Our study preliminarily suggested that the expression of hsa_circ_002059, hsa_circ_0000096 and hsa_circ_0001895 in serum might be correlated with gastric cancer.

Objective To investigate the predictive value of baseline neutrophil-to-lymphocyte ratio (NLR) in the curative effect and prognosis of breast cancer patients treated with neoadjuvant chemotherapy.Methods The clinical data of 304 breast cancer patients received neoadjuvant chemotherapy in Beijing Cancer Hospital during 2010 were retrospectively analyzed.The correlations of baseline NLR with clinicopathological parameters of breast cancer patients were analyzed by Wilcox or Kruskal-Wallis tests,and the correlation of NLR with pathologic complete response (pCR) after neoadjuvant chemotherapy was analyzed by the binary logistic regression.The effect of clinic pathological parameters on the disease-free survival(DFS) of the patients was evaluated by the univariable and muhivariable Cox regression models.Results The medians of NLR in pCR + patients (n =62) and pCR-patients (n =242) were 1.76 and 1.72,respectively,and there was no significant difference between themn (P ＞ 0.05).Multivariate analysis indicated that the TNM stage (P ＜ 0.05) and pCR (P ＜ 0.05) were the independent risk factors influencing the prognosis of breast cancer patients.There was no significant correlation between NLR and 5-year DFS (HR=0.842,95％CI=0.566-1.255,P＞0.05).Condusion NLR lacks the predictive value in the curative effect and prognosis of breast cancer patients treated with neoadjuvant chemotherapy,while TNM stage and pCR are the independent risk factors influencing the prognosis of breast cancer patients.