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.

Background::The heavy metals cadmium (Cd) and mercury (Hg) are known to be widespread environmental contaminants and high occupational exposure adversely affects the risk of chronic kidney disease (CKD). However, evidence from epidemiological studies linking low Cd and Hg exposure (or non-industrial) to the risk of progression to CKD are conflicting. This study aimed to explore the association of low Cd and Hg exposure with the risk of CKD in Chinese adults aged ≥80 years.Methods::The participants were recruited for the Healthy Aging and Biomarkers Cohort Study in 2017, an ongoing perspective survey conducted in longevity areas in China initially involving 3016 older adults. We used logistic regression models to estimate odds ratios (ORs) with 95% confidence intervals of CKD setting Cd and Hg as categorical variables. Logistic regression with restricted cubic spline was used to characterize a dose-response relationships between Cd or Hg concentrations and the risk of CKD in the study population.Results::The ORs for the risk of CKD comparing the fourth to the first quartile of blood Cd, blood Hg, urine Cd, and urine Hg were 1.77, 1.57, 2.03, and 1.50, respectively. Restricted cubic spline models showed that blood Cd and urine Hg were significantly linearly correlated with the risk of CKD, while blood Hg and urine Cd were non-linearly correlated with the risk of CKD with a steeper slope at concentrations <2.30 μg/L and 3.30 μg/g creatinine.Conclusions::Our findings suggest that even low Cd and Hg exposure (or non-industrial) were associated with increased risk of CKD in Chinese oldest old, although we did not find a significant multiplicative and additive interaction between Cd and Hg levels in relation to the risk of CKD.

Objective:To examine the association of blood uric acid (UA) and cognitive impairment (CI) among oldest-old adults in China.Methods:Data was collected in 9 longevity areas of China from Healthy Aging and Biomarkers Cohort Study (HABCS) conducted during 2017-2018. Finally,1, 622 elderly aged 80 years and older with complete information on blood UA and cognitive function score were included in this study. Information on demographic characteristics, lifestyle, and health status were collected through questionnaire and physical examination. Venous blood samples of the participants were collected to test blood UA level. Cognitive impairment (CI) was assessed using the Chinese Mini-Mental State Examination (MMSE) according to personal educational level. Generalized Estimating Equations (GEE) model for binary data was used to analyze the association of blood UA and CI, and further compared the associations among different age and body mass index (BMI) groups.Results:Of the 1 622 oldest-old, the mean age was (92.2±8.1) years, 656 (40.4%) were male, the mean level of blood UA was (343.3±86.2) μmol/L, and 482 (29.7%) oldest-old had CI. Compared with the lowest quartile of UA, the risks of CI in the second, third and highest quartiles were gradually reduced, the corresponding ORs and 95% CI were 0.99 (0.71-1.33), 0.87 (0.68-0.94) and 0.69 (0.48-0.85), respectively; and the linear trend test was statistically significant ( P<0.001). Subgroup analysis showed that the effects of higher UA associated with lower risk of CI were stronger in younger oldest-old (aged 80-89 years) and thinner group (BMI<24) ( Pinteraction<0.05). Conclusions:Blood UA was negatively associated with the risk of having CI in the oldest-old among the nine longevity areas of China.

Objective:To investigate the association of blood oxidative stress level with hypertriglyceridemia in the elderly aged 65 years and older in China.Methods:A total of 2 393 participants aged 65 years and older were recruited in 9 longevity areas from Heathy Aging and Biomarkers Cohort Study, during 2017 to 2018. Information on demographics characteristic, life style and health status were collected by questionnaire and physical examination, and venous blood was collected to detect the levels of blood oxidative stress and hypertriglyceridemia. The linear or non-linear association between oxidative stress and hypertriglyceridemia was described by restrictive cubic splines (RCS) fitting multiple linear regression model. The generalized linear mixed effect model was conducted to assess the association between oxidative stress and hypertriglyceridemia.Results:A total of 2 393 participants, mean age was 84.6 years, the youngest was 65 and the oldest was 112, the male was 47.9%(1 145/2 393), the triglyceride level was (1.4±0.8) mmol/L. The hypertriglyceridemia detection rate was 9.99%(239/2 393). The results of multiple linear regression model with restrictive cubic spline fitting showed that MDA level was linear association with triglyceride level; SOD level was nonlinear association with triglyceride level. MDA level had significantly association with hypertriglyceridemia, and the corresponding OR value was 1.063 (95% CI: 1.046,1.081) with 1 nmol/ml increment of blood MDA; SOD level had significantly association with hypertriglyceridemia, and the corresponding OR value was 0.986(95% CI: 0.983,0.989) with 1 U/ml increment of blood SOD. Conclusion:Among the elderly aged 65 and older in 9 longevity areas in China, MDA and SOD levels were associated with the risk of hypertriglyceridemia.

Objective:To investigate the association between oxygen saturation (SpO 2) and risk of 3-year all-cause mortality among Chinese older adults aged 65 or over. Methods:The participants were enrolled from Healthy Aging and Biomarkers Cohort Study in year of 2012 to 2014 in 9 longevity areas in China. In this prospective cohort study, 2 287 participants aged 65 or over were enrolled. Data on SpO 2 and body measurements were collected at baseline in 2012, and data on survival outcome and time of mortality were collected at the follow-up in 2014. Participants were divided into two groups according to whether SpO 2 was abnormal (SpO 2<94% was defined as abnormal). Results:The 2 287 participants were (86.5±12.2) years old, 1 006 were males (44.0%), and 315 (13.8%) were abnormal in SpO 2. During follow-up in 2014, 452 were died, 1 434 were survived, and 401 were lost to follow-up. The all-cause mortality rate was 19.8%, and the follow-up rate was 82.5%. The mortality rate of SpO 2 in normal group was 21.1%, and that of abnormal group was 41.6% ( P<0.001). After adjusting for confounding factors, compared to participants with normal SpO 2, participants with abnormal SpO 2 had increased risk of all-cause mortality with HR (95% CI) of 1.62 (1.31-2.02); HR (95 % CI) was 1.49 (0.98-2.26) for males and 1.71 (1.30-2.26) for females in abnormal SpO 2group, respectively; HR (95% CI) was 2.70 (0.98-7.44) for aged 65-79 years old, 1.22 (0.63-2.38) for aged 80-89 years old, and 1.72 (1.35-2.19) for aged over 90 years old in abnormal SpO 2 group, respectively. Conclusion:Abnormal SpO 2 was responsible for increased risk of 3-year all-cause mortality among Chinese elderly adults.

Objective:To investigate the relationship between the neutrophil-to-lymphocyte ratio (NLR) and the risk of depression symptoms among older adults aged 65 and above in 9 longevity areas of China.Methods:Data was collected in 9 longevity areas of China from Healthy Aging and Biomarkers Cohort Study (HABCS) conducted between 2017 and 2018. Finally,2018 elderly aged 65 years and above with complete information on neutrophil count, lymphocyte count and depressive symptoms were included in this study. Information on demographic characteristics, lifestyle, and health status was collected through questionnaire and physical examination. Complete blood counts which included lymphocytes and neutrophils were obtained by testing venous blood samples. Participants were divided into four groups by the quartile of NLR level, i.e. Q1, Q2, Q3, Q4. Logistic regression model was applied to analyze the association of NLR with depression symptoms. Results:Among 2 018 older adults, the mean(±SD) age was 82.6(±10.73), 1 032(51.14%) were male, 390(19.33%) were detected with depressive symptoms. Compared with participants of NLR in the 1 st quartile, the OR(95% CI) of risk for depressive symptoms was 1.47 (0.99, 2.19), 1.67 (1.13, 2.47) and 1.95 (1.32, 2.89), respectively. Conclusion:Increased NLR level is significantly related to depressive symptoms among elderly aged 65 years and above 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 investigate the association of blood arsenic level with hyperuricemia among elderly aged 65 years and older.Methods:Data was collected in 9 longevity areas from Heathy Aging and Biomarkers Cohort Study between 2017 and 2018. 2 438 participants aged 65 years and older with complete information on blood arsenic and uric acid were included in this study. Information including demographics characteristic, life style and health status was collected by questionnaire and physical examination. Meanwhile, venous blood was collected to detect the levels of blood arsenic and uric acid. Subjects were stratified into three groups (low, middle and high) by tertiles of blood arsenic level. Logistic regression models were used to analyze the association of blood arsenic level with hyperuricemia.Results:The age of participants was (84.57±11.41) years, of which 1 172 (48.07%) were male and 1 525 (62.55%) were over 80 years old. The detection rate of hyperuricemia was 17.23% (420), and the detection rates of hyperuricemia were 11.77%, 19.25% and 20.62% among participants with low, middle and high blood arsenic, respectively ( P<0.001). After controlling confounding factors, compared with participants who had low blood arsenic, the ORs (95% CI) of hyperuricemia for the participants with middle and high blood arsenic were 1.57 (1.12-2.23) and 2.08 (1.46-2.99), respectively. Subgroups analysis showed that compared with female, the association between blood arsenic level and hyperuricemia was more obvious in males ( Pinteraction<0.05). Conclusion:Blood arsenic level is associated with the risk for hyperuricemia among the elderly aged 65 years and older in 9 longevity areas in China.

Objective:To examine the association of blood uric acid (UA) and cognitive impairment (CI) among oldest-old adults in China.Methods:Data was collected in 9 longevity areas of China from Healthy Aging and Biomarkers Cohort Study (HABCS) conducted during 2017-2018. Finally,1, 622 elderly aged 80 years and older with complete information on blood UA and cognitive function score were included in this study. Information on demographic characteristics, lifestyle, and health status were collected through questionnaire and physical examination. Venous blood samples of the participants were collected to test blood UA level. Cognitive impairment (CI) was assessed using the Chinese Mini-Mental State Examination (MMSE) according to personal educational level. Generalized Estimating Equations (GEE) model for binary data was used to analyze the association of blood UA and CI, and further compared the associations among different age and body mass index (BMI) groups.Results:Of the 1 622 oldest-old, the mean age was (92.2±8.1) years, 656 (40.4%) were male, the mean level of blood UA was (343.3±86.2) μmol/L, and 482 (29.7%) oldest-old had CI. Compared with the lowest quartile of UA, the risks of CI in the second, third and highest quartiles were gradually reduced, the corresponding ORs and 95% CI were 0.99 (0.71-1.33), 0.87 (0.68-0.94) and 0.69 (0.48-0.85), respectively; and the linear trend test was statistically significant ( P<0.001). Subgroup analysis showed that the effects of higher UA associated with lower risk of CI were stronger in younger oldest-old (aged 80-89 years) and thinner group (BMI<24) ( Pinteraction<0.05). Conclusions:Blood UA was negatively associated with the risk of having CI in the oldest-old among the nine longevity areas of China.