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*

Traditional Chinese medicine (TCM) serves as a treasure trove of ancient knowledge, holding a crucial position in the medical field. However, the exploration of TCM's extensive information has been hindered by challenges related to data standardization, completeness, and accuracy, primarily due to the decentralized distribution of TCM resources. To address these issues, we developed a platform for TCM knowledge discovery (TCMKD, https://cbcb.cdutcm.edu.cn/TCMKD/). Seven types of data, including syndromes, formulas, Chinese patent drugs (CPDs), Chinese medicinal materials (CMMs), ingredients, targets, and diseases, were manually proofread and consolidated within TCMKD. To strengthen the integration of TCM with modern medicine, TCMKD employs analytical methods such as TCM data mining, enrichment analysis, and network localization and separation. These tools help elucidate the molecular-level commonalities between TCM and contemporary scientific insights. In addition to its analytical capabilities, a quick question and answer (Q&A) system is also embedded within TCMKD to query the database efficiently, thereby improving the interactivity of the platform. The platform also provides a TCM text annotation tool, offering a simple and efficient method for TCM text mining. Overall, TCMKD not only has the potential to become a pivotal repository for TCM, delving into the pharmacological foundations of TCM treatments, but its flexible embedded tools and algorithms can also be applied to the study of other traditional medical systems, extending beyond just TCM.

OBJECTIVE To provide refere nce for the optimization and adjustment of the relevant policies in the field of pediatric drug in China. METHODS“Children”“pediatrics”and“drugs”were taken as the keywords to search the official websites of the State Council ，the National Health Commission ，the National Healthcare Security Administration ，the State Administration of Market Regulation and other relevant ministries and commissions ，and collect the relevant pediatric drug policies issued at the national level from January 1，2010 to December 31，2021. Content analysis method was used to summarize ，code and statistically analyze the policy tools used in the policy research documents. RESULTS A total of 39 policy documents and 327 policy tools were included in this study. According to statistics ，from 2011 to 2021，China issued national policy documents on pediatric drug use every year ，and in recent years ，the issuance of documents was relatively intensive. The main body of issuing pediatric drugs policy was the national health department and drug supervision and administration department （71.79％，28/39），and the number of documents issued by relevant ministries and commissions alone （76.92％，30/39）was significantly more than the number of documents jointly issued by multiple ministries and commissions （23.08％，9/39）. The environmental policy tools were the most widely used （64.83％，212/327），followed by s upply-oriented policy tools （30.28％，99/327），and demand-oriented policy tools were the least used （4.89％，16/327）. CONCLUSIONS The development of pediatric drug use in China is in its infancy. It is suggested that China should optimize supply-oriented policy tools，increase capital investment and the use of public health service tools ；adjust environmental policy tools ，accelerate the legislation of pediatric drugs ，and increase the proportion of incentive policy tool ；attach importance to demand-oriented policy tools ，strengthen international exchanges and the application of service outsourcing in the field of pediatric medication ；plan the use of various policy tools as a whole ，and coordinate the use proportion of three types of policy tool and their sub policy tools，so as to enhance the initiative of policy tools ，form policy synergy ，and jointly promote the development of pediatric drug use.

Objective:To evaluate the efficacy, safety, and pharmacokinetics of the generic azacitidine in Chinese patients with higher-risk myelodysplastic syndromes(MDS).Methods:Between October 2013 and 2016, 72 patients were eligible for enrollment at 9 sites from China received generic subcutaneous azacitidine 75 mg·m -2·d -1 for 7 days per 28-day cycle, for ≥6 cycles. Pharmacokinetic blood samples were collected on day 1 of a single-dose. Results:For each patient at cycle 6 or at the time of study discontinuation, whichever came first, the overall response rate, which included complete remission (CR)and partial remission(PR), was 6.9%(5/72), the rate of patients who had the best effect with CR or PR during the treatment was 12.5%(9/72). Patients who were dependent on red-blood-cell transfusions and platelet transfusions at baseline became transfusion independent were 46.3%(19/41)and 41.2% (7/17), respectively. The median time of treatment was 6 cycles, and the median OS was 16.1 months (95% CI 10.9-20.6 months). For 36 patients(50%)received treatment at ≥6 cycles, and the median OS was 22.3 months(95% CI 16.1- not evaluative). Most common grade Ⅲ-Ⅳ hematologic treatment-emergent adverse events were neutropenia(55%), leukopenia(47%), and thrombocytopenia(61%). Pharmacokinetic profiles were similar for generic and original azacitidine in Chinese patients. Conclusion:Generic azacitidine treatment was favorable and safe and can be used as a standard treatment for patients with higher-risk MDS.

Objective To explore the value of minimally invasive isthmic cerclage by laparoscope in the treatment of cervical insufficiency.Methods 22 patients with uterine insufficiency were selected,including 14 cases of non pregnancy and 8 cases of pregnancy,they all had transvaginal cervical cerclage surgery failure history,and took uterine minimalist cerclage by laparoscope,regularly followed-up and the clinical effect was observed.Results There were 14 cases of non-pregnancy,11 cases of post-operative pregnancy,35+3 to 40+3 weeks of gestation termination,average (38.6 ± 1.2) weeks of gestation,7 cases of gestation,37 +5 to 39 +4 weeks,mean (38.5 ±0.4) weeks.Conclusion Minimally invasive cervix cerclage by laparoscope is a good choice for those who have undergone transvaginal cerclage.

BACKGROUND:Total knee arthroplasty has matured in clinical treatment. LPS-Flex Mobile Bearing System (Zimmer, USA) artificial knee prosthesis is the high-flexion rotating platform type knee prosthesis. The time of its clinical application in China is short, so its advantages have not been reported. OBJECTIVE:To investigate the preliminary clinical outcome of the total knee arthroplasty with LPS-Flex Mobile Bearing system artificial knee prosthesis (Zimmer, USA), and to assess the biocompatibility of artificial prosthesis and host using range of motion of knee and function after replacement. METHODS:We retrospectively analyzed 37 patients (42 knees) undergoing total knee arthroplasty using Zimmer LPS-Flex Mobile Bearing prostheses (high-flexion rotating platform type knee prosthesis) in The First Hospital Affiliated to Soochow University from February 2012 to March 2014, including 9 males (10 knees) and 28 females (32 knees), aged 47-78 years, averagely 63.7 years. Bone cement fixation was used, and the patel a was not treated with replacement. Postoperative complications were observed. Ranges of motion of knee joint preoperatively and postoperatively were compared. The recovery of knee joint function was evaluated using Hospital for Special Surgery Knee Score. RESULTS AND CONCLUSION:A total of 34 cases (38 knees) were fol owed up for 6-28 months. Range of motion of knee joint improved from 88.5° before operation to 124.2° after operation on average. Hospital for Special Surgery Knee Score improved from 52.5 before replacement to 91.1 after replacement, showing significant differences (P<0.01). Therapeutic effects were assessed according to Hospital for Special Surgery Knee Score:excel ent in 20 cases, good in 16 cases, average in 2 cases, with an excel ent and good rate of 95%. The incidence of various complications was low. These data suggested that short-period clinical outcomes of high-flexion rotating platform type knee prosthesis replacement are satisfactory. This prosthesis has advantages in its design, which is more close to the physical structure of knee joint, but its long-period outcomes deserve further investigations.

Objective Paeoniflorin ( PAE) is a potential neuroprotective agent.In this study, we investigated the protective effect of PAE on cerebral ischemia/reperfusion ( CI/R) injury in gerbils and its underlying mechanisms. Methods The model of CI/R was established in 50 gerbils by bilateral common carotid occlusion for 10 min followed by 6-hour reperfusion.Then the animals were equally randomized into five groups:sham, model, 5 mg/kg PAE, 10 mg/kg PAE, and 20 mg/kg PAE.The latter three groups were treated with intraperitoneal injection of PAE once daily for 3 days before carotid occlusion, while the former two groups with saline only, all at 10 ml/kg.Stroke indexes were calculated during the reperfusion.The contents of endogenous neuropeptides, endothelin and calcitonin gene-related peptide ( CGRP) in the plasma were measured by radioimmunoassay.The levels of superoxide dismutase ( SOD) and malondialdehyde ( MDA) in the brain tissue homogenate were determined by the method of xanthine oxidase. Results The 5, 10, and 20 mg/kg PAE groups showed significantly decreased stroke index (14.8 ±3.6, 12.3 ±2.0, and 12.7 ±1.4) as compared with the model group (18.4 ±2.9) (P<0.05), but remarkably increased SOD activity ([99.30 ±9.71], [106.85 ± 15.13] , and [110.25 ±14.90] vs [86.54 ±10.22] nU/mgPro, P<0.05) .The MDA content was significantly lower in the 10 and 20 mg/kg PAE groups than in the model group ([69.23 ±8.42] and [65.91 ±7.64] vs [94.76 ±10.30] μmol/mgPro, P<0.01). The plasma endothelin level was markedly decreased in all the PAE groups in comparison with the model group ([24.06 ±5.37], [19.62 ±5.60] and [21.08 ±4.64] vs [30.52 ±7.13] ng/L, P<0.05). Conclusion The protective effect of PAE pretreatment in CI/R injury appears to be associated with the inhibition of the brain free radicals, lipid peroxidation and endothelin production.

OBJECTIVETo study the relationship between soluble resistance-related calcium-binding protein (sorcin) gene and multidrug resistance gene (mdr1), and their significance in clinical drug resistance and prognosis of acute myeloid leukemia (AML).

METHODSAmplification of sorcin gene and mdr1 gene in K562/A02 cell detected by Northern blot, were monitored by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) in 65 AML patients and 27 normal controls, with their relationship and clinical outcame analyzed.

RESULTSThe amplification of sorcin gene and mdr1 gene in AML patients were significantly higher than that in the normal control, which were related to clinical drug resistance and prognosis. The amplification of sorcin gene was related to the amplification of mdr1 gene in the two groups. The clinical drug resistance incidence rate and complete remission rate were 92.9% and 7.1% in sorcin(+)/mdr1(+) group. They were 8.6% and 91.4% in the sorcin(-)/mdr1(-) group (P < 0.001).

CONCLUSIONThe co-amplification of sorcin and mdr1 gene can be taken as a good indicator of clinical drug resistance and prognosis of AML.

ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; Acute Disease ; Blotting, Northern ; methods ; Calcium-Binding Proteins ; genetics ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Gene Expression ; Humans ; K562 Cells ; Leukemia, Myeloid ; genetics ; physiopathology ; Neoplasm Proteins ; genetics ; Prognosis

OBJECTIVETo study the relationship between the expression of soluble drug resistance-related calcium-binding protein (sorcin) gene and the clinical multidrug resistance in acute leukemia (AL).

METHODSA semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was used to investigate the transcription levels of the human sorcin gene in 95 AL patients and 27 controls.

RESULTSSorcin gene expression was significantly higher in AL patients than in normal contrls (P < 0.001), and higher in relapsed/refractory acute myeloid leukemia (AML) patients than in those newly diagnosed or in complete remission. Sorcin gene overexpression was significantly lower in non-resistant patients than in resistant ones (P < 0.001). CR rates of these two groups were 20.0% and 80.0%, respectively. Sorcin gene expression was higher in AML-M(5) patients than M(2), M(3), M(4) patients.

CONCLUSIONSorcin gene overexpression is significantly associated with clinical multidrug resistance and prognosis, it is one of the indicators for predicting prognosis of AL patients.

Acute Disease ; Calcium-Binding Proteins ; genetics ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Gene Expression ; Humans ; K562 Cells ; Leukemia, Myeloid ; genetics ; Neoplasm Proteins ; genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; Solubility

0.05),while those of the cells treated with 6?10-5,6?10-6,6?10-7 mol/L of exemestane were significantly different from that of controls(P