The glucagon receptor (GCGR) is a critical target for the treatment of metabolic disorders such as Type 2 Diabetes Mellitus (T2DM) and obesity. Activation of GCGR enhances systemic insulin sensitivity through paracrine stimulation of insulin secretion, presenting a promising avenue for treatment. However, the discovery of effective GCGR agonists remains a challenging and resource-intensive process, often requiring time-consuming wet-lab experiments to synthesize and screen potential compounds. Recent advances in artificial intelligence technologies have demonstrated great potential in accelerating drug discovery by streamlining screening and efficiently predicting bioactivity. In the present work, we propose DeepGCGR, a two-layer deep learning model that leverages graph convolutional networks (GCN) integrated with a multiple attention mechanism to expedite the identification of GCGR agonists. In the first layer, the model predicts the bioactivity of various compounds against GCGR, efficiently filtering large chemical libraries to identify promising candidates. In the second layer, DeepGCGR classifies high bioactive compounds based on their functional effects on GCGR signaling, identifying those with potential agonistic or antagonistic effects. Moreover, DeepGCGR was specifically applied to identify novel GCGR-regulating compounds for the treatment of T2DM from natural products derived from traditional Chinese medicine (TCM). The proposed method will not only offer an effective strategy for discovering GCGR-targeting compounds with functional activation properties but also provide new insights into the development of T2DM therapeutics.
Deep Learning ; Drug Discovery/methods* ; Humans ; Diabetes Mellitus, Type 2/metabolism* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology*

The anterior cruciate ligament (ACL) reconstruction mostly relies on the experience of surgeons. To improve the effectiveness and adaptability of the tension after ACL reconstruction in knee joint rehabilitation, this paper establishes a lateral force measurement model with relaxation characteristics and designs an on-line stiffness measurement system of ACL. In this paper, we selected 20 sheep knee joints as experimental material for the knee joint stability test before the ACL reconstruction operation, which were divided into two groups for a comparative test of single-bundle ACL reconstruction through the anterolateral approach. The first group of surgeons carried out intraoperative detection with routine procedures. The second group used ACL on-line stiffness measurement system for intraoperative detection. After that, the above two groups were tested for postoperative stability. The study results show that the tension accuracy is (- 2.3 ± 0.04)%, and the displacement error is (1.5 ± 1.8)%. The forward stability, internal rotation stability, and external rotation stability of the two groups were better than those before operation (
Animals ; Anterior Cruciate Ligament/surgery* ; Anterior Cruciate Ligament Injuries/surgery* ; Anterior Cruciate Ligament Reconstruction ; Biomechanical Phenomena ; Cadaver ; Joint Instability/surgery* ; Knee Joint/surgery* ; Range of Motion, Articular ; Rotation ; Sheep

Objective:To evaluate the impact of colonoscopy on the incidence of colorectal cancer (CRC).Methods:This study was based on the Screening Project of Early Diagnosis and Treatment of CRC in Jiashan county, Zhejiang province. After excluding participants with incomplete information, these with individual history of CRC, those with CRC, enteritis or ulcer, noticed through colonoscopy exam at baseline, a total of 25 894 participants were finally included. Cox proportional hazards regression model was used to analyze the association between colonoscopy and the incidence of CRC.Results:This study was followed up for 160 113 person-years with a median of 5.67 years. During the follow-up period, 127 of them developed the CRC. The incidence rates of CRC in participants, were 202.35 per 100 000 person-years, 40.93 per 100 000 person-years and 63.62 per 100 000 person-years, respectively among the following three groups: who did not take the colonoscopy, without colorectal lesions or with benign colorectal lesions noticed by the colonoscopy and the differences were statistically significant ( P<0.05). After adjusting for potential confounding factors, the HRs(95 %CI) of CRC were 0.24 (0.16-0.36) and 0.29 (0.17-0.49), among those who did not have or had colorectal lesions in the participants who underwent the colonoscopy. Stratified by anatomic site, age and sex, results showed that the associations among the aforementioned groups were relatively stable. Conclusion:Colonoscopy could effectively contribute to the reduction of CRC incidence in the high-risk population.

Objective: To explore the correlation between obesity and the risk of colorectal adenoma, so as to provide theoretic evidence for the intervention of the high-risk population for colorectal cancer. Methods: Based on the Screen Project of Early Diagnosis and Treatment of Colorectal Cancer in Jiashan County, from August 2012 to March 2018, the results of colonoscopy and body measurement information of the high-risk population for colorectal cancer were collected. According to the results of colonoscopy, 3 895 patients with colorectal adenoma and 11 232 healthy controls were enrolled. Multivariate logistic regression was used to analyze the correlation between overweight (body mass index (BMI) 24.0 to 27.9 kg/m²), obesity (BMI≥28.0 kg/m²) and the risk of colorectal adenoma. Results: After adjusting for gender and age, compared with that of individuals with normal weight (BMI 18.5 to 23.9 kg/m²), the risk of colorectal adenoma of obese patients increased by 36% (odds ratio (OR)=1.36, 95% confidence interval (CI) 1.18 to 1.56). After stratifing by gender, compared with that of individuals with normal weight, the risk of colorectal adenoma of obese males increased by 30% (OR=1.30, 95%CI 1.07 to 1.59), the risk of colorectal adenoma of overweight females and obese females increased by 15% (OR=1.15, 95%CI 1.01 to 1.31) and 40% (OR=1.40, 95%CI 1.14 to 1.71), respectively. After stratifing by age, compared with that of individuals with normal weight, the risk of colorectal adenoma of obese patients aged between 40 and 59 years increased by 31% (OR=1.31, 95%CI 1.07 to 1.61), and the risk of colorectal adenoma of overweight and obese patients aged between 60 and 74 years increased by 13% (OR=1.13, 95%CI 1.01 to 1.27) and 39% (OR=1.39, 95%CI 1.15 to 1.70), respectively. The results of subgroup analysis according to pathological types indicated that the risk of non-advanced adenoma and advanced adenoma of obese patients increased by 35% (OR=1.35, 95%CI 1.16 to 1.57) and 39% (OR=1.39, 95%CI 1.06 to 1.83), respectively. Conclusions Obesity is correlated with colorectal adenoma, which is more significant in women, individuals aged between 60 and 74 years and advanced adenoma. The intervention of high-risk population for colorectal cancer should include body mass control.