Background/Aims: The utility of Baveno-VII criteria of clinically significant portal hypertension (CSPH) to predict decompensation in compensated advanced chronic liver disease (cACLD) patient needs validation. We aim to validate the performance of CSPH criteria to predict the risk of decompensation in an international real-world cohort of cACLD patients. Methods: cACLD patients were stratified into three categories (CSPH excluded, grey zone, and CSPH). The risks of decompensation across different CSPH categories were estimated using competing risk regression for clustered data, with death and hepatocellular carcinoma as competing events. The performance of “treating definite CSPH” strategy to prevent decompensation using non-selective beta-blocker (NSBB) was compared against other strategies in decision curve analysis. Results: One thousand one hundred fifty-nine cACLD patients (36.8% had CSPH) were included; 7.2% experienced decompensation over a median follow-up of 40 months. Non-invasive assessment of CSPH predicts a 5-fold higher risk of liver decompensation in cACLD patients (subdistribution hazard ratio, 5.5; 95% confidence interval, 4.0–7.4). “Probable CSPH” is suboptimal to predict decompensation risk in cACLD patients. CSPH exclusion criteria reliably exclude cACLD patients at risk of decompensation, regardless of etiology. Among the grey zone, the decompensation risk was negligible among viral-related cACLD, but was substantially higher among the non-viral cACLD group. Decision curve analysis showed that “treating definite CSPH” strategy is superior to “treating all varices” or “treating probable CSPH” strategy to prevent decompensation using NSBB. Conclusions Non-invasive assessment of CSPH may stratify decompensation risk and the need for NSBB in cACLD patients.

Peptide-drug conjugates (PDCs) are the next generation of targeted therapeutics drug after antibody-drug conjugates (ADCs), with the core benefits of enhanced cellular permeability and improved drug selectivity. Two drugs are now approved for market by US Food and Drug Administration (FDA), and in the last two years, the pharmaceutical companies have been developing PDCs as targeted therapeutic candidates for cancer, coronavirus disease 2019 (COVID-19), metabolic diseases, and so on. The therapeutic benefits of PDCs are significant, but poor stability, low bioactivity, long research and development time, and slow clinical development process as therapeutic agents of PDC, how can we design PDCs more effectively and what is the future direction of PDCs? This review summarises the components and functions of PDCs for therapeutic, from drug target screening and PDC design improvement strategies to clinical applications to improve the permeability, targeting, and stability of the various components of PDCs. This holds great promise for the future of PDCs, such as bicyclic peptide‒toxin coupling or supramolecular nanostructures for peptide-conjugated drugs. The mode of drug delivery is determined according to the PDC design and current clinical trials are summarised. The way is shown for future PDC development.

Objective:To investigate the association between blood lead concentrations and cognition impairment among Chinese older adults aged 65 or over.Method:Data was collected in 9 longevity areas from Heathy Aging and Biomarkers Cohort Study between 2017 and 2018. This study included 1 684 elderly aged 65 years and older. Information about demographic characteristics, socioeconomic factors, health status and cognitive function score of respondents were collected by questionnaire survey and physical examination. Venous blood of the subjects was collected to detect the blood lead concentration. Subjects were stratified into four groups ( Q 1- Q 4) by quartile of blood lead concentration. Multivariate logistic regression model was used to analyze the association between blood lead concentration and cognitive impairment. The linear or non-linear association between blood lead concentration and cognitive impairment were described by restrictive cubic splines (RCS). Results:Among the 1 684 respondents, 843 (50.1%) were female and 191 (11.3%) suffered from cognition impairment. After adjusting for confounding factors, the OR value and 95% CI of cognition impairment was 1.05 (1.01-1.10) for every 10 μg/L increase in blood lead concentration in elderly; Compared with the elderly in Q 1, the elderly with higher blood lead concentration had an increased risk of cognitive impairment. The OR value and 95% CIof Q2, Q3 and Q4 groups were 1.19 (0.69-2.05), 1.45 (0.84-2.51) and 1.92 (1.13-3.27), respectively. Conclusion:Higher blood lead concentration is associated with cognitive impairment among the elderly aged 65 years and older in 9 longevity areas in China.

Objective:To investigate the association between blood lead concentrations and cognition impairment among Chinese older adults aged 65 or over.Method:Data was collected in 9 longevity areas from Heathy Aging and Biomarkers Cohort Study between 2017 and 2018. This study included 1 684 elderly aged 65 years and older. Information about demographic characteristics, socioeconomic factors, health status and cognitive function score of respondents were collected by questionnaire survey and physical examination. Venous blood of the subjects was collected to detect the blood lead concentration. Subjects were stratified into four groups ( Q 1- Q 4) by quartile of blood lead concentration. Multivariate logistic regression model was used to analyze the association between blood lead concentration and cognitive impairment. The linear or non-linear association between blood lead concentration and cognitive impairment were described by restrictive cubic splines (RCS). Results:Among the 1 684 respondents, 843 (50.1%) were female and 191 (11.3%) suffered from cognition impairment. After adjusting for confounding factors, the OR value and 95% CI of cognition impairment was 1.05 (1.01-1.10) for every 10 μg/L increase in blood lead concentration in elderly; Compared with the elderly in Q 1, the elderly with higher blood lead concentration had an increased risk of cognitive impairment. The OR value and 95% CIof Q2, Q3 and Q4 groups were 1.19 (0.69-2.05), 1.45 (0.84-2.51) and 1.92 (1.13-3.27), respectively. Conclusion:Higher blood lead concentration is associated with cognitive impairment among the elderly aged 65 years and older in 9 longevity areas in China.

Objective: To analyze influencing factors for depressive symptoms in the elderly aged 65 years and older in 8 longevity areas in China. Methods: We recruited 2 180 participants aged 65 years and older in 8 longevity areas from Healthy Aging and Biomarkers Cohort Study, a sub-cohort of the Chinese Longitudinal Healthy Longevity Survey in 2017. Multivariate logistic regression analysis was performed to evaluate the relationships of socio-demographic characteristics, behavioral lifestyle, chronic disease prevalence, functional status, family and social support with depressive symptoms in the elderly. Results: The detection rate of depression symptoms was 15.0% in the elderly aged 65 years and older in 8 longevity areas of China, and the detection rate of depression symptoms was 11.5% in men and 18.5% in women. Multivariate logistic regression analysis results showed that the detection rate of depressive symptoms was lower in the elderly who had regular physical exercises (OR=0.44, 95%CI: 0.26-0.74), frequent fish intakes (OR=0.57, 95%CI: 0.39-0.83), recreational activities (OR=0.65, 95%CI: 0.44-0.96), social activities (OR=0.28, 95%CI: 0.11-0.73) and community services (OR=0.68, 95%CI: 0.50-0.93). The elderly who were lack of sleep (OR=2.04, 95%CI: 1.49-2.80), had visual impairment (OR=1.54, 95%CI: 1.08-2.18), had gastrointestinal ulcer (OR=2.97, 95%CI: 1.53-5.77), had arthritis (OR=2.63, 95%CI: 1.61-4.32), had higher family expenditure than income (OR=1.80, 95%CI: 1.17-2.78) and were in poor economic condition (OR=4.58, 95%CI: 2.48-8.47) had higher detection rate of depressive symptoms. Conclusion The status of doing physical exercise, fish intake in diet, social activity participation, sleep quality or vision, and the prevalence of gastrointestinal ulcers and arthritis were associated with the detection rate of depressive symptoms in the elderly.

Objective To investigate the relationship between Ezrin expression and subcellular localization of E?cadherin(E?cad),and explore the clinical significance of this relationship to pathological features such as lymph nodes metastasis in breast cancer. Methods Ninety four cases of breast cancer tissue samples with lymph node metastasis were collected. The expression of Ezrin and E?cad was detected by immunohistochemi?cal method. Results The positive rates of and E?cad and Ezrin were respectively 45.7%and 58.5%in 94 nodes positive breast cancer,containing membranal expression of E?cad(E?cadm)in 20 cases and cytoplasmic expression of E?cad(E?cadc)in 23 cases;the frequency of E?cadc positive staining was significantly higher in Ezrin(+)tissues than that in Ezrin(-)tissues(P=0.025);E?cad expression level was significantly lower in TNMⅡ?Ⅲstage cases(P=0.001),and Ezrin expression(P=0.036)and E?cadc(P=0.013)was significantly increased in bigger cases;com?pared with E?cad(+),Ezrin(-),E?cadm tissues,the number of lymph node metastasis in E?cad(-)(P=0.011),Ezrin(+)(P=0.002),E?cadc (P=0.020)tissues were increased significantly;in the order of E?cad(+)/Ezrin(-),E?cad(-)/Ezrin(-),E?cad(+)/Ezrin(+),and E?cad(-)/Ezrin(+),the number of lymph node metastasis was increased significantly(P<0.001);similarly,in the order of E?cadm/Ezrin(-),E?cadc/Ezrin(-),E?cadm/Ezrin(+),and E?cadc/Ezrin(+),the number of lymph node metastasis was increased significantly(P=0.007). Conclusion Ezrin may regulate the subcellular localization of E?cad in metastatic breast cancer ,which may affect the course of breast cancer and promote the metastasis of lymph nodes.

Objective To study the preventive effect ofω-6 soybean oil fatty emulsion on gastric ulcer caused by acetic acid in rat model, and investigate its mechanisms. Methods Thirty healthy rats were randomly and equally assigned to the following 3 groups:sham operation,gastric ulcer,andω-6 Soybean oil fatty emulsion group.The model was induced by acetic acid. Five days after the model was established successfully,rats in ω-6 soybean oil group received the treatment by tail intravenous injection with the dose of 10 mL.kg-1 .d-1 ,the sham operation group and gastric ulcer group were given the same dose of 0.9%sodium chloride solution.The rats were sacrificed at 10th day after the treatment.The pathological changes of rat gastric ulcer tissue were observed by HE staining, and the concentration of gastric acid was detected by acid-base neutralization method,as well as the activity of pepsin was detected by colorimetry.Serum NO concentration was detected with nitrate reductive enzymatic method, and the expression of EGFR in gastric mucosal was detected with immunohistochemical method. Results Gastric ulcer area inω-6 soybean oil fatty emulsion group (5.67±2.32 mm2) was significantly lower than that in gastric ulcer group(8.68±1.98 mm2). The concentration of gastric acid (1.70±0.53 mmol.L-1), activity of pepsin(23.12±6.97 U) and NO level (64.62±13.86μmol.L-1 ) inω-6 soybean oil fatty emulsion group were much lower than those in the model control group.While the expression of EGFR in gastric ulcer tissue was increased after treatment withω-6 soybean oil fatty emulsion. Conclusion ω-6 soybean oil fatty emulsion exerts significant promotion effect on the healing of gastric ulcer,and its mechanism might be related to inhibiting the level of gastric acid, pepsin and NO, while improving the protective effect of EGFR on gastric mucosa.

Objective To evaluate the expression and relationship of miR-100 and FZD-8, one of the major compo?nents of Wnt signaling pathway, and the correlation of their expressions with lymph node metastasis in patients with breast cancer. Methods The expression of miR-100 was determined in 50 samples of human breast cancer tissues and adjacent normal tissues by in situ hybridization. The correlation of miR-100 expression with lymph node metastasis was analyzed by Mann-Whitney U test. The expression of FZD-8 was measured in 50 samples of human breast cancer tissues and adjacent normal tissues by immunohistochemistry. The correlation of the miR-100 expression with the protein expression of FZD-8 was evaluated by Pearson rank analysis. Results The expression of miR-100 was significantly lower in human breast can?cer tissues than that in adjacent normal breast tissues [2.00 (1.00, 3.00) vs. 6.00 (3.50, 8.00)]. The miR-100 expression was lower in patients with lymph node metastasis than that in patients without lymph node metastasis [1.50 (1.00, 2.75) vs. 3.00 (2.00, 4.00)]. The expression of FZD-8 was significantly higher in human breast cancer tissues than that in adjacent normal breast tissues [8.00 (6.00, 9.00) vs. 6.00 (3.75, 9.00)]. The miR-100 expression was negatively correlated with the FZD-8 pro?tein expression in human breast cancer tissues (rs=-0.592, P<0.001). Conclusion The miR-100, as an anti-metastasis-miRNA, may involve in the metastasis of breast cancer, which may be related with the regulation of the expression of FZD-8.

Objective To explore the clinical significance of Ezrin and β?catenin in breast cancer. Methods Immunohistochemical staining method was adopted to detect Ezrin and β?catenin protein expression level in 145 cases of breast cancer tissues,and their correlation with clinical data and prognosis of breast cancer was analyzed. Results Ezrin was expressed in 70 cases(48.3%),β?catenin was expressed in 82 cases (56.6%),and there was significantly negative correlation(r=0.267,P=0.001). The higher histologic grade of breast cancer,the higher expres?sion level of Ezrin(P=0.007),and the lower expression level of β?catenin(P<0.001). Ezrin expression level was increased significantly(P=0.027),but β?catenin expression level was reduced significantly(P=0.011)in lymph node positive breast cancer tissue. Ezrin expression was sig?nificantly correlated with shorter overall survival(P=0.004)and disease free survival(P=0.017)of breast cancer patients,but β?catenin expres?sion was significantly correlated with longer overall survival(P<0.001)and disease free survival(P=0.001)of breast cancer patients. However , Ezrin and β?catenin were not the independent risk factors of breast cancer patients as determined by multivariate Cox regression. Conclusion Ez?rin was significantly negative correlated with β?catenin in breast cancer. They play a role in the progression and poor prognosis of breast cancer , which can be used as breast cancer treatment targets.

This article proposes a novel occupational practice model implied from the native concept of Taiji Diagram. Four elements of Taiji Diagram, namely Yang-fish, Yin-fish, Yin-fish-eye and Yang-fish-eye, are matched to the elements of occupational practice, namely person, environment, economic condition and mental condition, respectively. The interaction between persons and their environment can be thought as the interaction between Yin and Yang, and the balance would be focused on. Some different ideas may be brought from this model, such as Appropriate Challenge, Appropriate Empowerment.