AIM To test the safety and effectiveness of hypertonic saline solution(HSS + F) as a strategy for weight loss andprevention of further deterioration of renal function.METHODS Patients admitted with acute decompensated...AIM To test the safety and effectiveness of hypertonic saline solution(HSS + F) as a strategy for weight loss andprevention of further deterioration of renal function.METHODS Patients admitted with acute decompensated heart failure(ADHF) who received HSS + F were included in the study. After a period of a standard ADHF treatment, our patients received an intravenous infusion of furosemide(250 mg) combined with HSS(150 mL of 3% NaCl) twice a day for a mean duration of 2.3 d. Our primary outcomes were weight loss and a change in serum creatinine per day of treatment. The parameters of the period prior to treatment with HSS + F were compared with those of the period with HSS + F. RESULTS A total of 47 patients were included. The mean creatinine on admission was 155 μmol/L ± 65 μmol/L, the ejection fraction was 40% ± 17%. The experimental treatment(HSS + F) resulted in greater weight loss per day of treatment than the standard treatment(-1.4 kg/d ± 1.4 kg/d vs-0.4 kg/d ± 1.0 kg/d, P = 0.0168). Importantly, the change in creatinine was not significantly different.CONCLUSION This study supports the effectiveness of HSS + F on weight loss in patients with ADHF. The safety profile, particularly with regard to renal function, leads us to believe that HSS + F may be a valuable option for those patients presenting with ADHF who do not respond to conventional treatment with intravenous furosemide alone.展开更多
Deep learning(DL)is currently revolutionizing peptide drug development due to both computational advances and the substantial recent expansion of digitized biological data.However,progress in oligopeptide drug develop...Deep learning(DL)is currently revolutionizing peptide drug development due to both computational advances and the substantial recent expansion of digitized biological data.However,progress in oligopeptide drug development has been limited,likely due to the lack of suitable datasets and difficulty in identifying informative features to use as inputs for DL models.Here,we utilized an unsupervised deep learning model to learn a semantic pattern based on the intrinsically disordered regions of~171 known osteogenic proteins.Subsequently,oligopeptides were generated from this semantic pattern based on Monte Carlo simulation,followed by in vivo functional characterization.A five amino acid oligopeptide(AIB5P)had strong bone-formation-promoting effects,as determined in multiple mouse models(e.g.,osteoporosis,fracture,and osseointegration of implants).Mechanistically,we showed that AIB5P promotes osteogenesis by binding to the integrinα5 subunit and thereby activating FAK signaling.In summary,we successfully established an oligopeptide discovery strategy based on a DL model and demonstrated its utility from cytological screening to animal experimental verification.展开更多
OSTEOKINES IN INTER-ORGAN COMMUNICATIONS The concept of“organic wholeness”permeates all the fields of traditional Chinese medicine,which is also widely accepted by modern medicine.The wealth of knowledge regarding i...OSTEOKINES IN INTER-ORGAN COMMUNICATIONS The concept of“organic wholeness”permeates all the fields of traditional Chinese medicine,which is also widely accepted by modern medicine.The wealth of knowledge regarding inter-organ communications generated in the latest decades provided solid evidence that human physiology and pathophysiology involve systematic interactions between multiple organs or tissues.Therefore,advancing our understanding of the inter-organ communication process is believed to provide a new perspective for treating various human diseases.展开更多
文摘AIM To test the safety and effectiveness of hypertonic saline solution(HSS + F) as a strategy for weight loss andprevention of further deterioration of renal function.METHODS Patients admitted with acute decompensated heart failure(ADHF) who received HSS + F were included in the study. After a period of a standard ADHF treatment, our patients received an intravenous infusion of furosemide(250 mg) combined with HSS(150 mL of 3% NaCl) twice a day for a mean duration of 2.3 d. Our primary outcomes were weight loss and a change in serum creatinine per day of treatment. The parameters of the period prior to treatment with HSS + F were compared with those of the period with HSS + F. RESULTS A total of 47 patients were included. The mean creatinine on admission was 155 μmol/L ± 65 μmol/L, the ejection fraction was 40% ± 17%. The experimental treatment(HSS + F) resulted in greater weight loss per day of treatment than the standard treatment(-1.4 kg/d ± 1.4 kg/d vs-0.4 kg/d ± 1.0 kg/d, P = 0.0168). Importantly, the change in creatinine was not significantly different.CONCLUSION This study supports the effectiveness of HSS + F on weight loss in patients with ADHF. The safety profile, particularly with regard to renal function, leads us to believe that HSS + F may be a valuable option for those patients presenting with ADHF who do not respond to conventional treatment with intravenous furosemide alone.
基金This work was supported by grants from the National Science and Technology Major Project of China(2016YFC1102705)the National Natural Science Foundation Projects of China(8206113022,92049201,81770873,81822012,81771043,81802193,81970898)+1 种基金the Shanghai Academic Leader of Science and Technology Innovation Action Plan(20XD1424000)the Shanghai Experimental Animal Research Project of Science and Technology Innovation Action Plan(201409006400).
文摘Deep learning(DL)is currently revolutionizing peptide drug development due to both computational advances and the substantial recent expansion of digitized biological data.However,progress in oligopeptide drug development has been limited,likely due to the lack of suitable datasets and difficulty in identifying informative features to use as inputs for DL models.Here,we utilized an unsupervised deep learning model to learn a semantic pattern based on the intrinsically disordered regions of~171 known osteogenic proteins.Subsequently,oligopeptides were generated from this semantic pattern based on Monte Carlo simulation,followed by in vivo functional characterization.A five amino acid oligopeptide(AIB5P)had strong bone-formation-promoting effects,as determined in multiple mouse models(e.g.,osteoporosis,fracture,and osseointegration of implants).Mechanistically,we showed that AIB5P promotes osteogenesis by binding to the integrinα5 subunit and thereby activating FAK signaling.In summary,we successfully established an oligopeptide discovery strategy based on a DL model and demonstrated its utility from cytological screening to animal experimental verification.
基金supported by the National Natural Science Foundation of China(no.92049201).
文摘OSTEOKINES IN INTER-ORGAN COMMUNICATIONS The concept of“organic wholeness”permeates all the fields of traditional Chinese medicine,which is also widely accepted by modern medicine.The wealth of knowledge regarding inter-organ communications generated in the latest decades provided solid evidence that human physiology and pathophysiology involve systematic interactions between multiple organs or tissues.Therefore,advancing our understanding of the inter-organ communication process is believed to provide a new perspective for treating various human diseases.