ObjectiveTo generate cynomolgus and rhesus monkey models carrying the Booroola fecundity (FecB) variant of bone morphogenetic protein receptor type 1B (BMPR1B) gene (designated BMPR1B^FecB) using adenine base edit technology and to explore genetic improvement strategies for enhancing the reproductive performance of laboratory macaques. MethodsFour single-guide RNAs (sgRNAs) were designed to target the BMPR1B c.746A>G locus in cynomolgus and rhesus monkeys. The sgRNAs were combined with the ABE8e-SpRY base editor, and the resulting editing complexes were microinjected into zygotes of both macaque species. Following in vitro culture of the injected embryos, nested PCR amplification was performed to detect the base-editing efficiency at the target site to screen for highly efficient sgRNAs. Subsequently, normally developing gene-edited embryos were transferred into the oviducts of surrogates. Seven days after birth, ear skin or peripheral blood samples were collected from the newborn monkeys for genotyping and mosaicism analysis, and the growth, development, and health status of the gene-edited monkeys were monitored. ResultsAmong the four candidate sgRNAs, sgRNA4 was identified as achieving 100% editing efficiency at the c.746A>G site. A total of 17 live monkey offspring were obtained via embryo transfer, including 8 cynomolgus monkeys and 9 rhesus monkeys. Genotyping results showed that all 8 newborn cynomolgus monkeys carried the c.746A>G point mutation, with an editing efficiency of 100% (8/8), of which 37.50% (3/8) were mosaics. Among the 9 newborn rhesus monkeys, 8 individuals carried the c.746A>G mutation, with an editing efficiency of 88.89% (8/9), of which 75.00% (6/8) were mosaics. ConclusionThe ABE8e-SpRY base-editing system enables precise editing at the c.746A>G (p.Q249R) locus of the BMPR1B gene in both cynomolgus and rhesus monkey embryos, resulting in the successful establishment of laboratory monkey models carrying the BMPR1B^FecB variant. These models provide a valuable foundation for future studies of the regulatory role of the BMPR1B^FecB variant in reproductive performance at the non‑human primate level, as well as for exploring genetic improvement strategies to enhance reproductive performance in laboratory monkeys.

There is increasing evidence that the activation of glucagon-like peptide-1 receptor(GLP-1R)can be used as a therapeutic intervention for cognitive disorders.Here,we have screened GLP-1 R targeted com-pounds from Scutellaria baicalensis,which revealed baicalein is a potential GLP-1 R small-molecule agonist.Mitophagy,a selective autophagy pathway for mitochondrial quality control,plays a neuro-protective role in multiple cognitive impairment diseases.We noticed that Glp1r knock-out(KO)mice present cognitive impairment symptoms and appear worse in spatial learning memory and learning capacity in Morris water maze(MWM)test than their wide-type(WT)counterparts.Our mechanistic studies revealed that mitophagy is impaired in hippocampus tissue of diabetic mice and Glp1r KO mice.Finally,we verified that the cognitive improvement effects of baicalein on diabetic cognitive dysfunction occur through the enhancement of mitophagy in a GLP-1 R-dependent manner.Our findings shed light on the importance of GLP-1 R for cognitive function maintenance,and revealed the vital significance of GLP-1R for maintaining mitochondrial homeostasis.Furthermore,we identified the therapeutic potential of baicalein in the treatment of cognitive disorder associated with diabetes.

Rivaroxaban has been widely used for prevention and treatment of pulmonary embolism in adults due to the convenience of oral taking, rapid effect, less drug interaction, less influence by diet, no need of monitoring and fixed dose.However, its clinical application in children has been controversial.The EINSTEIN-Jr clinical trial and case reports at home and abroad have demonstrated the safety and effectiveness of Rivaroxaban in children with venous thrombus embolism.Therefore, Rivaroxaban can be considered as an alternative to standard anticoagulant therapy for children with venous thrombus embolism.This study reviews the application progress of Rivaroxaban in children with thromboembolic diseases.

Objective:To investigate the association between grip strength, rapid gait speed and cognition in people aged 50 and above in Shanghai.Methods:Cross-sectional data was collected from the World Health Organization (WHO) study on global ageing and adult health (SAGE) wave 1 (2009-2010). A questionnaire survey was conducted among 8 643 participants aged 50 years old and above selected by using multistage random cluster sampling strategies in Shanghai. Factor analysis was applied to evaluate and generate cognitive function overall score.Association between grip strength, rapid gait speed and cognition was examined by a two-level hierarchical linear model.Results:A total of 8 175 participants were included in this study, who were (62.9±9.7) years old, including 3 782 (46.3%) males. The average grip strength and rapid gait speed of participants were (27.46±12.01) kg and (1.44±0.43) m/s respectively. The average scores of verbal recall (VR), verbal fluency (VF), forward digit span (FDS), backward digit span (BDS) and total cognitive scores were (5.72±0.09), (12.67±0.35), (6.84±0.10), (4.32±0.14) and (60.50±0.95) respectively. Grip strength was positively associated with VR, VF, FDS, BDS and overall cognition (standardized β =0.036, 0.079, 0.042, 0.046 and 0.043 respectively, P<0.05), and rapid gait speed was also positively associated with VR, VF and overall cognition (standardized β=0.040, 0.031, 0.039 respectively, P<0.05) after adjusted for age, sex, residence, education level, marital status, household income, co-morbidity of chronic conditions, BMI, drinking, smoking, fruits, vegetables intake and physical activities. Conclusion:Grip strength and rapid gait speed are both positively associated with cognitive function of people aged 50 and above, which would be indicators to evaluate their cognition.

Objective:To investigate the association between grip strength, rapid gait speed and cognition in people aged 50 and above in Shanghai.Methods:Cross-sectional data was collected from the World Health Organization (WHO) study on global ageing and adult health (SAGE) wave 1 (2009-2010). A questionnaire survey was conducted among 8 643 participants aged 50 years old and above selected by using multistage random cluster sampling strategies in Shanghai. Factor analysis was applied to evaluate and generate cognitive function overall score.Association between grip strength, rapid gait speed and cognition was examined by a two-level hierarchical linear model.Results:A total of 8 175 participants were included in this study, who were (62.9±9.7) years old, including 3 782 (46.3%) males. The average grip strength and rapid gait speed of participants were (27.46±12.01) kg and (1.44±0.43) m/s respectively. The average scores of verbal recall (VR), verbal fluency (VF), forward digit span (FDS), backward digit span (BDS) and total cognitive scores were (5.72±0.09), (12.67±0.35), (6.84±0.10), (4.32±0.14) and (60.50±0.95) respectively. Grip strength was positively associated with VR, VF, FDS, BDS and overall cognition (standardized β =0.036, 0.079, 0.042, 0.046 and 0.043 respectively, P<0.05), and rapid gait speed was also positively associated with VR, VF and overall cognition (standardized β=0.040, 0.031, 0.039 respectively, P<0.05) after adjusted for age, sex, residence, education level, marital status, household income, co-morbidity of chronic conditions, BMI, drinking, smoking, fruits, vegetables intake and physical activities. Conclusion:Grip strength and rapid gait speed are both positively associated with cognitive function of people aged 50 and above, which would be indicators to evaluate their cognition.

The analysis of big data in medical field cannot be isolated from the high quality clinical database, and the construction of first aid database in our country is still in the early stage of exploration. This paper introduces the idea and key technology of the construction of multi-parameter first aid database. By combining emergency business flow with information flow, an emergency data integration model was designed with reference to the architecture of the Medical Information Mart for Intensive Care III (MIMIC-III), created by Computational Physiology Laboratory of Massachusetts Institute of Technology (MIT), and a high-quality first-aid database was built. The database currently covers 22 941 medical records for 19 814 different patients from May 2015 to October 2017, including relatively complete information on physiology, biochemistry, treatment, examination, nursing, etc. And based on the database, the first First-Aid Big Data Datathon event, which 13 teams from all over the country participated in, was launched. The First-Aid database provides a reference for the construction and application of clinical database in China. And it could provide powerful data support for scientific research, clinical decision making and the improvement of medical quality, which will further promote secondary analysis of clinical data in our country.
Big Data ; Critical Care ; Databases, Factual ; Humans ; Medical Informatics

Objective:To explore the necessity of the preventive use of antibiotics and the effects of age and operation time on the efficacy of inguinal hernia repair without tension,and to elucidate the clinical significance of the preventive application of prophylactic antibiotics in inguinal hernia repair without tension.Methods:A total of 228 patients with inguinal hernia repair without tension were selected,amomg them 42 cases with high infection factors were treated with antibiotics (treated group),and 186 cases were not treated with antibiotics(untreated group) during the preoperative period.The prophylactic antibiotics were given 30 min before surgery,and the conventional dose was not used more than 48 h after surgery.All the cases were treated with artificial repair materials for the procedure of inguinal hernial repair without tension.The age,highest body temperature,white blood cell count,operation time,hospitalization time,and postoperative body temperature of all the 228 cases were recorded and analyzed statistically.Results:The preoperative and postoperative white blood cell counts had significant differences between the patients<60 years and the patients≥60 years in untreated group (P<0.05);there were no significant differences in the operation time,hospitalization time and body temperature between the patients<60 years and the patients≥60 years in untreated group (P>0.05).Compared with the patients with the operation time>90 min,the white blood cell count and hospitalization time of the patients with the operation time ≤90 min were increased (P<0.05).There were no significant differences of the body temperature and age between the patients with the operation time >90 min and the patients with the operation time≤90 min (P>0.05).The white blood cell count,operation time,hospitalization time and postoperative body temperature of the patients between treated group and untreated group had no significant differences (P>0.05).Conclusion:The use of antibiotics in the high-risk patients and non-use of antibiotics in the majority of elective inguinal hernia repair without tension can ensure the safe and performability of the patients.