As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

Objective To explore the clinical value of artificial intelligence (AI) quantitative parameters in distinguishing pathological grades of stageⅠ invasive adenocarcinoma (IAC). Methods Clinical data of patients with clinical stageⅠ IAC admitted to Yantaishan Hospital Affiliated to Binzhou Medical University from October 2018 to May 2023 were retrospectively analyzed. Based on the 2021 WHO pathological grading criteria for lung adenocarcinoma, IAC was divided into gradeⅠ, grade Ⅱ, and grade Ⅲ. The differences in parameters among the groups were compared, and logistic regression analysis was used to evaluate the predictive efficacy of AI quantitative parameters for grade Ⅲ IAC patients. Parameters were screened using least absolute shrinkage and selection operator (LASSO) regression analysis. Three machine learning models were constructed based on these parameters to predict grade Ⅲ IAC and were internally validated to assess their efficacy. Nomograms were used for visualization. Results A total of 261 IAC patients were included, including 101 males and 160 females, with an average age of 27-88 (61.96±9.17) years. Six patients had dual primary lesions, and different lesions from the same patient were analyzed as independent samples. There were 48 patients of gradeⅠ IAC, 89 patients of grade Ⅱ IAC, and 130 patients of grade Ⅲ IAC. There were statitical differences in the AI quantitive parameters such as consolidation/tumor ratio (CTR), ect among the three goups. (P<0.05). Univariate analysis showed that the differences in all variables except age were statistically significant (P<0.05) between the group gradeⅠ+grade Ⅱand the group grade Ⅲ . Multivariate analysis suggested that CTR and CT standard deviation were independent risk factors for identifying grade Ⅲ IAC, and the two were negatively correlated. Grade Ⅲ IAC exhibited advanced TNM staging, more pathological high-risk factors, higher lymph node metastasis rate, and higher proportion of advanced structure. CTR was positively correlated with the proportion of advanced structures in all patients. This correlation was also observed in grade Ⅲ but not in gradeⅠand grade ⅡIAC. CTR and CT median value were selected by using LASSO regression. Logistic regression, random forest, and XGBoost models were constructed and validated, among which, the XGBoost model demonstrated the best predictive performance. Conclusion Cautious consideration should be given to grade Ⅲ IAC when CTR is higher than 39.48% and CT standard deviation is less than 122.75 HU. The XGBoost model based on combined CTR and CT median value has good predictive efficacy for grade Ⅲ IAC, aiding clinicians in making personalized clinical decisions.

Intestinal aging is central to systemic aging, characterized by a progressive decline in intestinal structure and function. The core mechanisms involve dysregulation of epithelial cell renewal and gut microbiota dysbiosis. In addition to previous results in model organisms like Drosophila melanogaster, recent studies have shown that in mammalian models, aging causes increased intestinal permeability and intestinal-derived systemic inflammation, thereby affecting longevity. Therefore, anti-intestinal aging can be an important strategy for reducing frailty and promoting longevity. There are three key gaps remaining in the study of intestinal aging: (1) overemphasis on aging-related diseases rather than the primary aging mechanisms; (2) lack of specific drugs or treatments to prevent or treat intestinal aging; (3) limited aging-specific dysbiosis research. In this review, the basic structures and renewal mechanisms of intestinal epithelium, and mechanisms and potential therapies for intestinal aging are discussed to advance understanding of the causes, consequences, and treatments of age-related intestinal dysfunction.

Objective:To evaluate the feasibility of low radiation dose and low contrast dosage in coronary CT angiography (CCTA) of class I obese patients.Methods:This prospective study enrolled 57 patients (male/female, 50/7, age, 25-77 years) with body mass index (BMI) of 30-38 kg/m 2 and body weight of 85-119 kg scheduled for CCTA from August 2022 to March 2023 in our hospital. The patients were divided into two groups: control group (group A, n = 20) and low-dose group (group B, n = 37). Group A employed a standard-dose protocol: tube voltage 120 kVp and IDR 2.2 g I/s, while group B were scanned using the low-dose protocol: tube voltage 100 kVp and IDR 1.5 g I/s. Images in Group A and Group B were reconstructed with hybrid iterative reconstruction (HIR) at strength 4 and 8, respectively. Other scanning and reconstruction parameters were the same in two groups. Methods:The image quality was assessed by measuring the CT values and noise in the aortic root, left anterior descending artery and right coronary artery, and the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. Subjective image quality was evaluated for vessels according to the 18-segment classification system using a 4-point scale (1. poor, 4. excellent). The effective dose E and contrast dosage were compared. Statistical analysis was performed using independent samples t-test, Mann-Whitney U test or χ 2 test. Results:The BMI of groups A and B were 31.89 (30.77, 33.81) and 31.22 (30.46, 32.83) kg/m 2, respectively ( P>0.05). No statistically significant differences in CT values, noise, SNR, CNR were noticed between the two groups (all P>0.05). The mean subjective score of all coronary artery segments in the two groups were not less than 3, meeting the requirement of clinical diagnosis. There was no statistically significant difference in the overall subjective image quality between the two groups ( P>0.05). The radiation dose E in groups A and B were 7.58 and 4.49 mSv, respectively ( Z=-5.46, P<0.05). The contrast dosage in groups A and B were 66 and 45 ml, respectively. The radiation dose E and contrast dosage in group B were 41% and 32% lower than that in group A, respectively. Conclusions:For class I obese patients, it was feasible to use a low tube voltage (100 kVp) and low IDR (1.5 gI/s) protocol in CCTA. Radiation dose and contrast dosage can be reduced reasonably without compromising the CCTA image quality.

Objective To explore the distribution and drug resistance of pathogenic bacteria of infectious diseases in a grade-A tertiary hospital from 2020 to 2022.Methods The clinical data of totally 1 928 children with infectious diseases admitted to a grade-A tertiary hospital from 2020 to 2022 were retrospectively ana-lyzed.Bacterial identification and drug susceptibility tests were performed on sputum,blood,feces,secretions,urine and cerebrospinal fluid samples of all children after admission,and then the distribution of pathogenic bacteria and drug resistance were statistically analyzed.Results In this study,a total of 1 928 strains of non-repeating pathogens were isolated from a grade-A tertiary hospital from 2020 to 2022,and the pathogens were mainly isolated from the sputum(67.17％),followed by blood(12.03％),feces(11.00％),secretions(6.48％),urine(2.70％)and cerebrospinal fluid(0.62％).Among the 1 928 strains,1 202 gram-negative strains(62.34％)were mainly Haemophilus influenzae and Moraxella catarrhal,accounting for 24.17％and 15.82％respectively.There were 726 strains of gram-positive bacteria(37.66％),mainly streptococcus pneu-moniae and Staphylococcus aureus,accouting for 21.59％and 12.29％respectively.In addition,the pathogens in 2020-2022 accounted for 32.57％(628/1 928),38.43％(741/1 928)and 28.99％(559/1 928),respective-ly.The resistance rates of Haemophilus influenzae to ampicillin/sulbactam,cotrimoxazole,sulfamethoxazole/trimethoprim were more than 65.00％.The resistance rates of Moraxella catarrhal to cotrimoxazole,ampicil-lin/sulbactam were more than 40.00％.The resistance rates of Streptococcus pneumoniae to clindamycin,pen-icillin,sulfamethoxazole/trimethoprim and erythromycin were more than 87.00％.The resistance rates of Staphylococcus aureus to clindamycin,erythromycin and penicillin were more than 47.00％,and the resistance rate to penicillin was 88.61％.Conclusion From 2020 to 2022,the pathogens of infectious diseases in a grade-A tertiary hospital are mainly gram-negative bacteria,and there are different degrees of resistance to common-ly used clinical antibiotics.Therefore,in clinical practice,nosocomial infection prevention and control measures should be strictly implemented,antibiotics should be used carefully,and antibiotics could be selected reasona-bly according to the distribution characteristics of children's infection and drug sensitivity test results,which is of great significance for the prevention of hospital infectious diseases.

Objective:Farfarae Flos has the effect of cough suppression and phlegm elimination,with cough suppression as the main function.Studies have revealed that certain components of Farfarae Flos may be related to its cough suppressant effect,and some components have been confirmed to have cough suppressant activity.However,the antitussive material basis of Farfarae Flos has not been systematically elucidated.This study aims to elucidate the group of active ingredients in Farfarae Flos with cough suppressant activity by correlating the high performance liquid chromatography(HPLC)fingerprint of Farfarae Flos extract with its cough suppressant activity. Methods:HPLC was used to establish the fingerprint profiles of 10 batches of Farfarae Flos extract and obtain their chemical composition data.Guinea pigs were selected as experimental animals and the citric acid-induced cough model was used to evaluate the antitussive efficacy data of 10 batches of Farfarae Flos extract.SPF-grade healthy male Hartley guinea pigs were randomly divided into the S1 to S10 groups,a positive control group,and a blank control group(12 groups in total),with 10 guinea pigs in each group.The S1 to S10 groups were respectively administered Farfarae Flos extract S1 to S10(4 g/kg),the positive control group was administered pentoverine citrate(10 mg/kg),and the blank control group was administered purified water.Each group received continuous oral administration for 5 days.The guinea pigs were placed in 5 L closed wide-mouth bottles,and 17.5%citric acid was sprayed into the bottle with an ultrasonic atomizer at the maximum spray intensity for 0.5 minutes.The cough latency period and cough frequency in 5 minutes were recorded for each guinea pig.Grey relational analysis(GRA)and partial least squares regression(PLSR)were used to conduct spectral-effect correlation analysis of the chemical composition data of Farfarae Flos extract and the antitussive efficacy data,and predict the group of active ingredients in Farfarae Flos with antitussive activity.The bioequivalence verification was conducted to verify the predicted group of active ingredients in Farfarae Flos with antitussive activity:SPF-grade healthy male Hartley guinea pigs were randomly divided into a S9 group,an active ingredient group,a positive control group,and a blank control group(4 groups in total),with 10 guinea pigs in each group.The S9 group was administered Farfarae Flos extract S9(4 g/kg),the active ingredient group was administered the predicted combination of antitussive active ingredients(dose equivalent to 4 g/kg of Farfarae Flos extract S9),the positive control group was administered pentoverine citrate(10 mg/kg),and the blank control group was administered purified water.Each group received continuous oral administration for 5 days,and animal modeling and observation of efficacy indicators were the same as above. Results:The HPLC fingerprint of 10 batches of Farfarae Flos extract was established,and the peak area data of 14 main common peaks were obtained.The antitussive effect data of 10 batches of Farfarae Flos extract were obtained.Compared with the blank control group,the cough latence in the positive control group and S1,S2,S3,S4,S6,S7,S8,S9,S10 groups was prolonged(all P<0.01),while the cough frequency in 5 minutes in the positive control group and S1,S2,S4,S6,S8,S9,S10 groups was decreased(all P<0.05).The analysis of spectrum-effect relationship revealed that isochlorogenic acid C,isochlorogenic acid A,chlorogenic acid,isochlorogenic acid B,isoquercitrin,and rutin had high contribution to the antitussive effect of Farfarae Flos,and the 6 components were predicted to be the antitussive component group of Farfarae Flos.The verification of bioequivalence showed that there were no statistically significant differences in the antitussive effect between the S9 group and the antitussive component composition group(all P>0.05),which confirmed that isochlorogenic acid C,isochlorogenic acid A,chlorogenic acid,isochlorogenic acid B,isoquercetin,and rutin were the antitussive component group of Farfarae Flos. Conclusion:The analysis of spectrum-effect relationship combined with the verification of bioequivalence could be used to study the antitussive material basis of Farfarae Flos.The antitussive effect of Farfarae Flos is the result of the joint action of many components.

Objective:To discuss the effect of oridonin on the proliferation,migration,epithelial-mesenchymal transition(EMT),and apoptosis of the human nasopharyngeal carcinoma HONE-1 cells,and to clarify its related antitumor mechanism.Methods:The HONE-1 cells were treated with different concentrations(0,5,10,20,40,80,and 160 mg·L-1)of oridonin for 48 h.CCK-8 method was used to detect the inhibitory rates of proliferation of the cells in various groups and the drug concentration for subsequent experiment was confirmed.The HONE-1 cells were divided into control group,3 mg·L-1 oridonin group,and 6 mg·L-1 oridonin group.After 24 and 48 h of culture,CCK-8 method was used to detect the proliferation activities of the cells in various groups;5-ethynyl-2'-deoxyuridine(EdU)method was used to detect the rates of EdU-positive cells in various groups;colony formation assay was used to detect the numbers of clone formation in the cells in various groups;Transwell chamber experiment and cell wound assay were used to detect the numbers of migration cells and the scratch healing rates of the cells in various groups;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of cyclin-dependent kinase 1(CDK1)and cyclin-dependent kinase 4(CDK4)mRNA in the cells in various groups;Western blotting method was used to detect the expression levels of E-cadherin,Vimentin,Caspase-3,and poly ADP-ribose polymerase 1(PARP1)proteins in the cells in various groups.Results:The CCK-8 method results showed that the half-maximal inhibitory concentration(IC50)of oridonin at 48 h was 12.18 mg·L-1,and 1/4 IC50 and 1/2 IC50 values were used as the concentrations for subsequent experiments.Compared with control group,after treated for 24 and 48 h,the proliferation activities of the cells in 3 and 6 mg·L-1 oridonin groups were decreased(P＜0.05 or P＜0.01),the rate of EdU-positive cells were decreased(P＜0.05 or P＜0.01),the numbers of clone formation and migraton cells were decreased(P＜0.05 or P＜0.01),the scratch healing rates were decreased(P＜0.05 or P＜0.01),the expression levels of CDK1 and CDK4 mRNA in the cells were decreased(P＜0.05 or P＜0.01),the expression levels of E-cadherin,Caspase-3,and PARP1 proteins were increased(P＜0.05 or P＜0.01),and the expression levels of Vimentin protein were decreased(P＜0.05).Conclusion:Oridonin can inhibit the proliferation,clone formation,and migration of the human nasopharyngeal carcinoma HONE-1 cells by downregulating the expression of cell cycle-related proteins and EMT,and promote the apoptosis to exert an antitumor effect.

Objective:To assess the prognostic impact of frailty on elderly inpatients with heart failure.Methods:This prospective cohort study enrolled 121 in elderly patients with heart failure from Beijing Hospital, the General Hospital of the People's Liberation Army, and Beijing Tsinghua Changgung Hospital between September 2018 and April 2019.Patients were assessed for frailty using the Fried frailty phenotype and categorized into frail and non-frail groups.Follow-ups were conducted at 3-, 6-, and 12-months post-enrollment through clinic visits or phone calls to record adverse events.Composite endpoints include all-cause mortality and rehospitalization duo to deterioration of heart failure.Results:The study included 121 patients with an average age of 78.0±7.4 years, of whom 71(58.7%)were male and 57(47.1%)were classified as frail.Compared to the non-frail group, the frail group had lower estimated glomerular filtration rates[49.5±20.7 ml/(min·1.73m 2) vs.(64.0±27.1)ml/(min·1.73m 2)], lower scores in Basic Activities of Daily Living[5.0(4.0, 6.0) vs.6.0(5.0, 6.0)], Instrumental Activities of Daily Living[2.0(1.3, 7.8) vs.7.0(5.0, 8.0)], and Mini-Mental State Examination[26.0(16.0, 28.0) vs.27.0(22.3, 29.0)], all P<0.05.They also experienced longer hospital stays[10.5(6.0, 18.8)days vs.8.0(6.0, 11.8)days, P=0.008].During the follow-up period, the incidence of composite endpoint events was significantly higher in the frail group(43.9% vs.25.0%, P=0.029).Kaplan-Meier survival analysis demonstrated that the one-year incidence of composite endpoint events was significantly higher in the frail group( P=0.013).Multivariable Cox regression analysisindicated that frailty was an independent risk factor for composite endpoint events( HR=2.201, 95% CI: 1.089-4.447, P=0.028). Conclusions:Frailty is an independent risk factor for poor outcomes in elderly hospitalized patients with heart failure and should be considered a crucial factor in clinical assessment and treatment strategies.