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*

Objective:To investigate the effectiveness and safety of lacosamide (LCM) in pregnant women with epilepsy.Methods:A retrospective study was conducted involving 6 pregnant women with epilepsy who were treated with LCM at the Electroencephalogram Monitoring Center of the Department of Neurology, Xijing Hospital of Air Force Military Medical University from January 2022 to June 2023. Their electroclinical characteristics, seizures during pregnancy, breastfeeding, and follow-up were summarized.Results:The 6 patients were aged 22 to 30 years at the time of pregnancy. Three patients were treated with monotherapy, with a daily dose of LCM ranging from 150 mg to 200 mg, while the other 3 patients were treated with combination therapy, with a daily dose of 150 mg. The seizures of 5 patients decreased during pregnancy compared with progestation except for the case 2 without adherence to Medication. No malformations were observed in the newborns, with the Apgar scores of 9-10 at 1 minute and 5 minutes after birth. The infants showed normal growth, development, intelligence, and motor skills in subsequent assessments. Two patients breastfed their infants, 1 for 6 months and the other for 14 months by the last follow-up, with a daily LCM dose of 150 mg to 300 mg during the breastfeeding. No adverse reactions were observed in the infants.Conclusion:The addition of LCM during pregnancy and lactation showed good effectiveness and safety, with no observed birth malformations.

Background and Aims:Intrahepatic cholangiocarcinoma(ICC)is a highly malignant liver tumor,with an increasing incidence worldwide,particularly in Asia.Although radical surgical resection is currently the only potentially curative treatment,the high recurrence rate and low postoperative overall survival(OS)rate of ICC remain major clinical challenges.Adjuvant therapy(AT)and neoadjuvant therapy(NAT)are important strategies to reduce postoperative recurrence and prolong OS.Several studies have shown certain efficacy of these treatments.However,the specific efficacy and safety of combined NAT and AT in ICC treatment require further validation.This study was conducted to evaluate the value of combining NAT and AT in improving the therapeutic outcomes of ICC patients through a multicenter retrospective analysis,so as to provide scientific evidence for optimizing treatment strategies.Methods:The clinicopathologic data of 576 patients with ICC who underwent radical resection and were pathologically confirmed from 13 hospitals in China between December 2011 and December 2017 were retrospectively collected.Patients were grouped based on their treatment modality:NAT+AT group,AT group,and non-NAT/AT group.The three patient groups were matched pairwise in a 1∶1 ratio using propensity score matching(PSM)to balance baseline data.The Kaplan-Meier method was used to analyze OS and disease-free survival(DFS),and subgroup analyses were conducted according to the 8th edition of the AJCC TNM staging system.Results:A total of 395 ICC patients were included in the final analysis,with 42 patients(10.6%)in the NAT+AT group,62 patients(15.7%)in the AT group,and 291 patients(73.7%)in the non-NAT/AT group.Before PSM,significant differences were observed between groups in terms of CA19-9,liver function Child-Pugh classification,intraoperative blood loss,surgical margin,differentiation grade,vascular invasion,ECOG score,and lymph node dissection ratio(all P<0.05).After PSM,there were no significant differences in baseline characteristics between the groups(all P>0.05).After matching,the median OS and DFS in the NAT+AT group were significantly better than in the AT and non-NAT/AT groups(both P<0.05),while there were no significant differences in OS and DFS between the AT and non-NAT/AT groups(both P>0.05).Subgroup analysis showed that in TNM stage I patients,DFS in the NAT+AT group was significantly better than in the non-NAT/AT group(P<0.05),but OS was not significantly different(P>0.05).In TNM stage Ⅱ and Ⅲ patients,both OS and DFS in the NAT+AT and AT groups were significantly better than in the non-NAT/AT group(both P<0.05),and DFS in the NAT+AT group was significantly better than in the AT group in TNM stage Ⅲ patients(P<0.05).Conclusion:NAT combined with AT provides better survival benefits for patients with locally advanced ICC,but its benefit for early-stage ICC patients is limited.However,the retrospective design and sample size limitations of this study may affect the stability of the results,and future large-sample,multicenter,prospective studies are needed for further validation.

Objective To retrospectively analyze multicenter data from domestic sources, aiming to explore the link between intrahepatic cholangiocarcinoma (ICC) tumor size and prognosis, establishing a classification system based on tumor size. Methods Between December 2011 and September 2018, 280 ICC patients from 13 hospitals were included. The tumor size prognosis cutoff was identified by the minimum P-value method, and the classification's overall survival related effectiveness was assessed by Kaplan-Meier analysis. Results All 280 patients were divided into the group of tumor maximum diameter ≤4 cm and >4 cm. Tumor size was confirmed as an independent prognosis factor by multivariate COX regression analysis (HR=2.110, 95% CI: 1.358-3.280). Conclusions The tumor size dichotomy classification system based on the Chinese patient group can expediently predict ICC prognosis and offers an important basis for selecting post-operative individualized adjuvant therapy and follow up plans.

Translational therapy for liver cancer,as an emerging treatment strategy,is driving advancements in the management of intermediate and advanced liver cancer.Through continuous exploration by experts nationwide,translational therapy for liver cancer has reached a consensus,providing valuable scientific guidance for clinical practice.However,as treatment methods continue to evolve,translational therapy still faces numerous urgent challenges,particularly in areas such as personalized treatment,efficacy evaluation,and combined therapeutic strategies.These issues have become contentious and hotly debated topics,creating a situation where"consensus and controversy coexist,and opportunities and challenges intersect."To address these challenges,experts in the field of liver cancer must strengthen collaboration and communication,promote high-quality basic and clinical research,and continuously refine treatment protocols in practice,ultimately offering patients more scientific and precise therapeutic options.

Background and Aims:Intrahepatic cholangiocarcinoma(ICC)is a highly malignant liver tumor,with an increasing incidence worldwide,particularly in Asia.Although radical surgical resection is currently the only potentially curative treatment,the high recurrence rate and low postoperative overall survival(OS)rate of ICC remain major clinical challenges.Adjuvant therapy(AT)and neoadjuvant therapy(NAT)are important strategies to reduce postoperative recurrence and prolong OS.Several studies have shown certain efficacy of these treatments.However,the specific efficacy and safety of combined NAT and AT in ICC treatment require further validation.This study was conducted to evaluate the value of combining NAT and AT in improving the therapeutic outcomes of ICC patients through a multicenter retrospective analysis,so as to provide scientific evidence for optimizing treatment strategies.Methods:The clinicopathologic data of 576 patients with ICC who underwent radical resection and were pathologically confirmed from 13 hospitals in China between December 2011 and December 2017 were retrospectively collected.Patients were grouped based on their treatment modality:NAT+AT group,AT group,and non-NAT/AT group.The three patient groups were matched pairwise in a 1∶1 ratio using propensity score matching(PSM)to balance baseline data.The Kaplan-Meier method was used to analyze OS and disease-free survival(DFS),and subgroup analyses were conducted according to the 8th edition of the AJCC TNM staging system.Results:A total of 395 ICC patients were included in the final analysis,with 42 patients(10.6%)in the NAT+AT group,62 patients(15.7%)in the AT group,and 291 patients(73.7%)in the non-NAT/AT group.Before PSM,significant differences were observed between groups in terms of CA19-9,liver function Child-Pugh classification,intraoperative blood loss,surgical margin,differentiation grade,vascular invasion,ECOG score,and lymph node dissection ratio(all P<0.05).After PSM,there were no significant differences in baseline characteristics between the groups(all P>0.05).After matching,the median OS and DFS in the NAT+AT group were significantly better than in the AT and non-NAT/AT groups(both P<0.05),while there were no significant differences in OS and DFS between the AT and non-NAT/AT groups(both P>0.05).Subgroup analysis showed that in TNM stage I patients,DFS in the NAT+AT group was significantly better than in the non-NAT/AT group(P<0.05),but OS was not significantly different(P>0.05).In TNM stage Ⅱ and Ⅲ patients,both OS and DFS in the NAT+AT and AT groups were significantly better than in the non-NAT/AT group(both P<0.05),and DFS in the NAT+AT group was significantly better than in the AT group in TNM stage Ⅲ patients(P<0.05).Conclusion:NAT combined with AT provides better survival benefits for patients with locally advanced ICC,but its benefit for early-stage ICC patients is limited.However,the retrospective design and sample size limitations of this study may affect the stability of the results,and future large-sample,multicenter,prospective studies are needed for further validation.

Translational therapy for liver cancer,as an emerging treatment strategy,is driving advancements in the management of intermediate and advanced liver cancer.Through continuous exploration by experts nationwide,translational therapy for liver cancer has reached a consensus,providing valuable scientific guidance for clinical practice.However,as treatment methods continue to evolve,translational therapy still faces numerous urgent challenges,particularly in areas such as personalized treatment,efficacy evaluation,and combined therapeutic strategies.These issues have become contentious and hotly debated topics,creating a situation where"consensus and controversy coexist,and opportunities and challenges intersect."To address these challenges,experts in the field of liver cancer must strengthen collaboration and communication,promote high-quality basic and clinical research,and continuously refine treatment protocols in practice,ultimately offering patients more scientific and precise therapeutic options.

Objective:To investigate the effectiveness and safety of lacosamide (LCM) in pregnant women with epilepsy.Methods:A retrospective study was conducted involving 6 pregnant women with epilepsy who were treated with LCM at the Electroencephalogram Monitoring Center of the Department of Neurology, Xijing Hospital of Air Force Military Medical University from January 2022 to June 2023. Their electroclinical characteristics, seizures during pregnancy, breastfeeding, and follow-up were summarized.Results:The 6 patients were aged 22 to 30 years at the time of pregnancy. Three patients were treated with monotherapy, with a daily dose of LCM ranging from 150 mg to 200 mg, while the other 3 patients were treated with combination therapy, with a daily dose of 150 mg. The seizures of 5 patients decreased during pregnancy compared with progestation except for the case 2 without adherence to Medication. No malformations were observed in the newborns, with the Apgar scores of 9-10 at 1 minute and 5 minutes after birth. The infants showed normal growth, development, intelligence, and motor skills in subsequent assessments. Two patients breastfed their infants, 1 for 6 months and the other for 14 months by the last follow-up, with a daily LCM dose of 150 mg to 300 mg during the breastfeeding. No adverse reactions were observed in the infants.Conclusion:The addition of LCM during pregnancy and lactation showed good effectiveness and safety, with no observed birth malformations.

Hepatocellular carcinoma(HCC),commonly known as primary liver cancer,is a major cause of malignant tumors and cancer-related deaths in China,accounting for approximately 85％of all cancer cases in the country.Several guidelines have been used to diagnose and treat liver cancer.However,these guidelines provide a broad definition for classifying advanced liver cancer,with an emphasis on a singular approach,without considering treatment options for individual patients.Therefore,it is necessary to establish a comprehensive and practical expert consensus,specifically for China,to enhance the diagnosis and treatment of HCC using the Delphi method.The classification criteria were refined for Chinese patients with HCC,and the corresponding optimal treatment regimen recommendations were developed.These recommendations took into account various factors,including tumor characteristics,vascular tumor thrombus grade,distant metastasis,liver function status,portal hypertension,and the hepatitis B virus replication status of patients with primary HCC,along with treatment prognosis.The findings and rec-ommendations provide detailed,scientific,and reasonable individualized diagnosis and treatment strategies for clinicians.