Frailty is a complex aging syndrome characterized by diminished strength and physiological dysfunction.Early diagnosis of frailty is of great value in helping the elderly to improve the quality of life.However,specific bio-logical markers to diagnose frailty are still lacking.In recent years,moderate protein intake has been shown to be an effective intervention in the management of frailty in older adults,and the relationship between frailty and amino acid metabolism has received widespread attention.This review discusses recent advances in the study of the mecha-nisms by which amino acid metabolism affects frailty and provide new ideas for searching specific biomarkers of frailty.

Objective:To evaluate the immunogenicity, safety, and immune persistence of the sequential booster with the recombinant protein-based COVID-19 vaccine (CHO cell) in healthy people aged 18-84 years.Methods:An open-label, multi-center trial was conducted in October 2021. The eligible healthy individuals, aged 18-84 years who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, were recruited from Shangyu district of Shaoxing and Kaihua county of Quzhou, Zhejiang province. All participants were divided into three groups based on the differences in prime-boost intervals: Group A (3-4 months), Group B (5-6 months) and Group C (7-9 months), with 320 persons per group. All participants received the recombinant COVID-19 vaccine (CHO cell). Blood samples were collected before the vaccination and after receiving the booster at 14 days, 30 days, and 180 days for analysis of GMTs, antibody positivity rates, and seroconversion rates. All adverse events were collected within one month and serious adverse events were collected within six months. The incidences of adverse reactions were analyzed after the booster.Results:The age of 960 participants was (52.3±11.5) years old, and 47.4% were males (455). The GMTs of Groups B and C were 65.26 (54.51-78.12) and 60.97 (50.61-73.45) at 14 days after the booster, both higher than Group A′s 44.79 (36.94-54.30) ( P value<0.05). The GMTs of Groups B and C were 23.95 (20.18-28.42) and 27.98 (23.45-33.39) at 30 days after the booster, both higher than Group A′s 15.71 (13.24-18.63) ( P value <0.05). At 14 days after the booster, the antibody positivity rates in Groups A, B, and C were 91.69% (276/301), 94.38% (302/320), and 93.95% (295/314), respectively. The seroconversion rates in the three groups were 90.37% (272/301), 93.75% (300/320), and 93.31% (293/314), respectively. There was no significant difference among these rates in the three groups (all P values >0.05). At 30 days after the booster, antibody positivity rates in Groups A, B, and C were 79.60% (238/299), 87.74% (279/318), and 90.48% (285/315), respectively. The seroconversion rates in the three groups were 76.92% (230/299), 85.85% (273/318), and 88.25% (278/315), respectively. There was a significant difference among these rates in the three groups (all P values <0.001). During the sequential booster immunization, the incidence of adverse events in 960 participants was 15.31% (147/960), with rates of about 14.38% (46/320), 17.50% (56/320), and 14.06% (45/320) in Groups A, B, and C, respectively. The incidence of adverse reactions was 8.02% (77/960), with rates of about 7.50% (24/320), 6.88% (22/320), and 9.69% (31/320) in Groups A, B, and C, respectively. No serious adverse events related to the booster were reported. Conclusion:Healthy individuals aged 18-84 years, who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, have good immunogenicity and safety profiles following the sequential booster with the recombinant COVID-19 vaccine (CHO cell).

Background Dry eye is a common disease worldwide.Cyclosporine A(CsA) is provided to be a immunosuppressive agent and is effective on dry eye.But in China,0.05％ CsA is not yet applied in dry eye treatment.Objective This study was to evaluate the efficacy and safety of 0.05％ CsA eye drops in the treatment of dry eye.Methods This was a randomized,double-blind,vehicle-controlled parallel group study.Forty eyes of 40 patients with moderate to severe dry eye were randomly divided into two groups,with the corresponding treatment of 0.05％ CsA eye drops or the vehicle emulsion.The patients in both the groups received non-preserved artificial tear.Symptoms and signs were observed before administration,(7±1),(28±2),(56±3),and (84±3) days and also 14 days after withdrawal.The clinical effective rate was considered as the primary outcome.The subjective assessment of the patients including total symptom scores and ocular surface disease index (OSDI) scores,Schirmer Ⅰ test (S Ⅰ t) with topical anaesthesia,tear film breakup time (BUT),rose Bengal and fluorescein staining scores were evaluated.The safety profile was evaluated by adverse events,visual acuity and ocular tolerance.Results At the end of this trial,the ocular symptoms scores,conjunctival hyperemia,BUT,S Ⅰ t and keratoconjunctiva staining scores of the two groups had statistically significant difference.The total effective rate of 0.05％ CsA treatment group was 75％ (15/20) and vehicle group was 25％ (5/20).There was a statistically significant difference between groups (P =0.000),and the 95％ confidence interval (C1) of the difference value of total effectiveness between the two groups was 30.80％-53.75％.At the end of this trial,there was no statistically significant difference in visual acuity distribution (P =0.890).No obvious discomfort was found in the patients received 0.05％ CsA eye drops.There were no adverse events during the follow-up duration.Conclusions 0.05％ CsA ophthalmic emulsion is an effective and safe treatment for dry eyes.