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 evaluate the effect of Tai Chi and Qigong on patients with lumbar disc herniation (LDH). Methods: Relevant data were retrieved from nine English and Chinese databases, including Cochrane Library, PubMed, and Wanfang Data, etc. from inception to June 2024. All published randomized controlled trials assessing the effect of Tai Chi and Qigong on visual analog scale (VAS), Japanese Orthopedic Association (JOA) score, and other health indicators in participants with LDH compared to usual medical care or other treatments were included. Grey literature, trials involving the pushing of hands (Tui Shou) or Tai Chi with weapons, and trials with co-interventions (Tai Chi/Qigong plus another treatment) were excluded. Methodological quality was analyzed using the Cochrane risk of bias tool, and evidence quality was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) tool. Results: Fourteen trials (954 patients) were included in this study. Tai Chi and Qigong were associated with lower VAS pain scores (standardized mean difference −0.55, 95% confidence interval [CI] −0.95 to −0.15, P = .01), higher JOA scores (mean difference [MD] 4.40, 95% CI 2.62 to 6.18, P < .001) and straight leg raise test results (MD 9.40°, 95% CI 7.64 to 11.15, P < .001) in patients with LDH. Furthermore, compared with usual care, Tai Chi and Qigong showed enhanced effects on pain and JOA scores. When compared to other exercises or massage, the effect on pain scores was similar but that on JOA scores was significant. Conclusions Tai Chi and Qigong may have favorable effects on VAS pain and JOA scores compared with usual care, and on JOA scores compared with other exercises or massage in patients with LDH. Given the overall poor quality of the evidence, the results of current study should be interpreted cautiously.

Objective:To investigate the clinical characteristics and prognosis of Philadelphia (Ph) chromosome-positive chronic myeloid leukemia (CML) patients with additional chromosomal abnormalities.Methods:The data of 351 CML patients with Ph-positive in the Affiliated Hospital of Qingdao University from January 2009 to January 2019 were retrospectively analyzed. The bone marrow chromosomal karyotype analysis of all patients was performed by using R-banding technique. The clinical characteristics and karyotype of Ph-positive CML patients with additional chromosomal abnormalities at initial diagnosis were summarized, and Kaplan-Meier was used to analyze the differences in overall survival (OS) of patients with different karyotypes.Results:Among 351 patients with Ph-positive CML, 32 (9.1%) cases had variant translocation. At initial diagnosis, 47 cases had additional chromosomal abnormalities including 29 cases in chronic phase accounting for 9.15% (29/317) of all patients in chronic phase, 3 cases in accelerated phase accounting for 25.00% (3/12) of all patients in accelerated phase, 15 cases in blast crisis accounting for 68.18% (15/22) of all patients in blast crisis; there was a statistically significant difference in the chromosomal abnormalities rate of all different phases ( χ2=50.799, P<0.05). Among 47 Ph-positive CML patients with additional chromosomal abnormalities, 13 patients had complex karyotypes with more than 3 additional chromosomal abnormalities, the proportion of complex karyotypes in chronic phase, accelerated phase and blast crisis was 13.79% (4/29), 33.33% (1/3) and 53.33% (8/15), respectively, and the difference was statistically significant ( χ2=9.26, P<0.05). The study showed that the most common additional chromosomal abnormalities in chronic phase were double Ph (48.28%, 14/29) and -Y (10.34%, 3/29), while the most common chromosomal abnormalities in the blast crisis were +8 (26.67%, 4/15) and double Ph (26.67%, 4/15). Kaplan-Meier survival analysis showed that at initial diagnosis the OS time of patients with additional chromosomal abnormalities was worse than that of those with the non-additional chromosomal abnormalities group ( χ2 = 61.138, P<0.05). The OS of patients with complex karyotypes for Ph - positive CML patients with additional chromosomal abnormalities at initial diagnosis was worse than that of patients with non-complex karyotypes, and the difference was significant ( χ2 = 4.945, P < 0.05). Conclusions:The additional chromosomal abnormalities is closely related to the progression of CML, and the prognosis of CML patients with additional chromosomal abnormalities is poorer than that of patients with only Ph translocation. Moreover, the more complex the additional chromosomes are, the more likely blastic changes are, and the poorer prognosis. And additional chromosomeal abnormalities during the treatment of CML patients may also lead to the progression of blastic changes.

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 investigate the effect of immunophenotyping on prognosis of multiple myeloma (MM) patients treated with bortezomib regimen as main treatment. Methods: Seventy-six MM patients in the Department of Hematology in the Affiliated Hospital of Qingdao University from January 2012 to January 2017 were retrospectively analyzed. The effects of the expressions of CD45, CD56 and other factors on progression free survival (PFS) and overall survival (OS) in MM patients treated with bortezomib-containing regimen were also analyzed. Results: Univariate analysis showed that statistical differences of the median PFS (12 months vs. 19 months, P < 0.001) and median OS (19 months vs. 23 months, P= 0.001) were significant in the group of CD45 positive and negative of MM patients; the median PFS (14 months vs. 21 months, P= 0.014) and median OS (16 months vs. 25 months, P= 0.026) for MM patients with hemoglobin (Hb) < 100 g/L and Hb ≥ 100 g/L were statistically significant; the median PFS (13 months vs. 18 months, P= 0.004) and median OS (14 months vs. 24 months, P= 0.008) for MM patients with albumin (ALB) < 35 g/L and ALB ≥ 35 g/L were statistically significant. The median PFS time and the median OS time in female MM patients were shorter than those in male MM patients (13 months vs. 19 months, P= 0.008; 16 months vs. 25 months, P= 0.008). Multivariate analysis showed that female and CD45 positive were the independent poor prognostic factors for PFS and OS in MM patients (P < 0.05). Conclusion CD45 positive and female are important prognostic factors for MM patients treated with bortezomib regimen as main treatment.

Objective: To investigate the efficacy and safety of IA regimen which contains idarubicin (IDA) 8 mg/m², 10 mg/m² or 12 mg/m² as induction chemotherapy for adult patients with de-novo acute myeloid leukemia (AML) . Methods: A total of 1 215 newly diagnosed adult AML patients, ranging from May 2011 to March 2015 in the First Affiliated Hospital of Soochow University and other 36 clinical blood centers in China were enrolled in the multicenter, single-blind, non-randomized, clinical controlled study. To compare the response rate of complete remission (CR) , adverse events between different dose idarubicin combined with cytarabine (100 mg/m²) as induction chemotherapy in newly diagnosed patients of adult AML. Results: Of 1 207 evaluable AML patients were assigned to this analysis of CR rate. The CR rates of IDA 8 mg/m² group, IDA 10 mg/m² group and IDA 12 mg/m² group were 73.6% (215/292) , 84.1% (662/787) and 86.7% (111/128) , respectively (P<0.001) . After adjusted for age, blast ratio of bone marrow, FAB classification and risk stratification, the odds ratios (95% CI) of IDA 10 mg/m² group and IDA 12 mg/m² group were 0.49 (0.34-0.70) and 0.36 (0.18-0.71) , as compared with the IDA 8 mg/m² group (P<0.001, P=0.003) . In the intermediate and favorable groups, CR rates was 76.5% (163/213) , 86.9% (506/582) and 86.1% (68/79) in different doses of IDA (P=0.007) . Interestingly, IA regimen with IDA 10 mg/m² was the only beneficial factor affecting CR in this group after adjusted for age, blast ratio of bone marrow and FAB classification[OR=0.47 (95% CI 0.31-0.71) , P<0.001]. CR rates in adverse group was 50.0% (18/36) , 60.6% (43/71) and 81.8% (18/22) respectively (P=0.089) . However, the odds ratios (95% CI) of IDA 12 mg/m² when compared with the IDA 8 mg/m² was 0.22 (0.06-0.80) , after adjusted for age, blast ratio of bone marrow and FAB classification. The median time (days) of neutrophil count less than 0.5×10⁹/L in IDA 8 mg/m² group, IDA 10 mg/m² group and IDA 12 mg/m² group were 14 (11-18) , 15 (11-20) and 18 (14-22) , respectively (P=0.012) and of platelet count lower than 20×10⁹/L were 14 (7-17) , 15 (11-20) and 17 (15-21) , respectively (P=0.001) . The incidences of lung infection in the three groups were 9.8%, 13.5% and 25.2%, respectively (P<0.001) . Conclusions For young adult patients (aged 18-60 years) with AML in China, intensifying induction therapy with idarubicin 10 mg/m² is clinically superior to IDA 8 mg/m² and IDA 12 mg/m² in favorable intermediate AML subgroup. However, idarubicin 12 mg/m² is more suitable to adverse AML subgroup.

Philadelphia chromosome-positive acute myeloid leukemia is controversial and difficult to distinguish from the blast phase of chronic myeloid leukemia.As a myeloid neoplasm,rare cases of this leukemia manifest multiple soft-tissue tumors or bone lytic lesions.In this paper,we describe a 49-year-old male patient who had an abrupt onset with sharp chest pain,fever,fatigue,emaciation,and splenomegaly.18F-fluoro-deoxy-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) result showed diffuse and uneven hypermetabolic lesions in the bone marrow with peripheral bone marrow expansion,multiple soft tissue neoplasms with high 18F-FDG uptake,and lytic bone lesions.Bone marrow smear and biopsy detected aberrant blast cells expressing myeloid rather than lymphoid immunophenotype marker.For the existence of Philadelphia chromosome and BCR-ABL1 fusion gene together with complex chromosome abnormalities,a diagnosis of Philadelphia-positive acute myeloid leukemia was made,although the type (de novo or blast crisis) remained unclear.

Objective To investigate the clinical characteristics and treatment efficacy in newly diagnosed multiple myeloma (MM). Methods The clinical data and treatment methods of 176 patients with newly diagnosed MM were retrospectively analyzed. Results The most common chief complaint in the patients with MM was bone pain. 26.1 % (46/176) patients once experienced misdiagnosis. The overall response rate (ORR) was 65.9 % (116/176), the ORR of bortezomib group (81.0 %, 34/42) was significantly higher than that of M2 regimen group (61.8 %, 34/55) and VAD regimen group (60.8 %, 48/79) (P<0.05). Between normal renal function subgroup and renal insufficiency subgroup in bortezomib group, the efficacy was no significant difference (P>0.05). The most common adverse reactions included hematologic toxicity, infection and peripheral neurotoxicity. Multiple organ failure was the main cause of death (47.1 %, 16/34). Conclusions The clinical manifestations of MM are complex and diverse, which is easy to be misdiagnosed. Molecular genetic abnormalities are closely related to prognosis. Proteasome inhibitor bortezomib can improve the curative effect and not be affected by renal function. To prolong the survival time of the patients needs to prevent and control the infection and renal insufficiency actively.