This study employs ultra-performance liquid chromatography(UPLC) to analyze the differences in alkaloid content of Commelina communis from various geographical origins, exploring its feasibility as a quality evaluation indicator. A total of 57 batches of C. communis samples from 23 provinces, autonomous regions, and municipalities in China were selected. The MicroPulite HSS T3(2.1 mm×50 mm, 1.8 μm)column was used with a mobile phase of acetonitrile-0.2% phosphoric acid aqueous solution(20∶80), detection wavelength at 254 nm, and a flow rate of 0.3 mL·min~(-1) to measure the content of 1-deoxynojirimycin(DNJ) and deoxymannojirimycin(DMJ). The MicroPulite XP tC_(18)(2.1 mm×100 mm, 1.7 μm)column was employed with a mobile phase of acetonitrile-0.2% phosphoric acid aqueous solution(4∶96), detection wavelength at 254 nm, and a flow rate of 0.4 mL·min~(-1) to measure the content of norharmine(NHM) and harmanme(HM). Chemometric methods were applied to study the relationships and differences among the 57 batches of C. communis. Significant differences in alkaloid content were observed among C. communis from different regions, with the average total content decreasing in the order of North China, Northeast China, Northwest China, East China, Southwest China, Central China, and South China. Cluster analysis(CA) and principal component analysis(PCA) further revealed the quality differences of C. communis from various origins, and partial least squares discriminant analysis(PLS-DA) identified DNJ as a marker compound to distinguish the quality differences between different geographical sources of C. communis. It is recommended that the content limit of DNJ be set at no less than 0.055 9%, providing a reference for the quality evaluation and clinical application of C. communis medicinal materials.
Alkaloids/analysis* ; Drugs, Chinese Herbal/chemistry* ; China ; Chromatography, High Pressure Liquid ; Chemometrics/methods* ; Quality Control

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*

Objectives:To evaluate the clinical value of the Paris system for reporting urinary cytology (TPS) in the diagnosis of urothelial carcinoma (UC).Methods:A total of 1 744 cytological diagnostic records (from 751 cases) were collected retrospectively. All specimens were voided urines and histopathology as the gold standard. The sensitivity and specificity of urinary cytological diagnosis of UC and risk of high grade malignant (ROHM) in each diagnostic category were compared.Results:There were 360 cases with histopathology. The percentage of negative for high-grade urothelial carcinoma (NHGUC) was 30.1% (226/751), atypical urothelial cells (AUC) was 29.8% (224/751), suspicious for high-grade urothelial carcinoma (SHGUC) was 16.8% (126/751), high grade urothelial carcinoma (HGUC) was 21.2% (159/751), and non-urothelial malignancy (NUM) was 2.1% (16/751). The histpathologic ROHM corresponding to each cytological diagnosis category were 27.3% for NHGUC, 32.7% for AUC, 74.7% for SHGUC, 96.6% for HGUC and 100.0% for NUM, respectively. ROHM of SHGUC was significantly higher than that of AUC group, and the difference between the two groups was statistically significant ( P＜0.001). ROHM of HGUC group was significantly higher than that of SHGUC group, and the difference was statistically significant ( P＜0.001). With SHGUC as the cut-off value, the sensitivity and specificity of cytological diagnosis of HGUC were 76.7% (165/215) and 85.7% (18/21), and with HGUC as the cut-off value, the sensitivity and specificity of cytological diagnosis of HGUC were 53.0% (114/215) and 100.0% (21/21), respectively. Conclusions:Urine cytology has high sensitivity and specificity in the diagnosis of HGUC. The malignant risk of TPS varies with different diagnosis category. The high malignant risk population in cancer hospital leads to the relatively high malignant proportion and ROHM in each diagnosis category. Urinary cytology TPS reporting system is helpful to clinical management and has good clinical application value.

Objectives:To evaluate the clinical value of the Paris system for reporting urinary cytology (TPS) in the diagnosis of urothelial carcinoma (UC).Methods:A total of 1 744 cytological diagnostic records (from 751 cases) were collected retrospectively. All specimens were voided urines and histopathology as the gold standard. The sensitivity and specificity of urinary cytological diagnosis of UC and risk of high grade malignant (ROHM) in each diagnostic category were compared.Results:There were 360 cases with histopathology. The percentage of negative for high-grade urothelial carcinoma (NHGUC) was 30.1% (226/751), atypical urothelial cells (AUC) was 29.8% (224/751), suspicious for high-grade urothelial carcinoma (SHGUC) was 16.8% (126/751), high grade urothelial carcinoma (HGUC) was 21.2% (159/751), and non-urothelial malignancy (NUM) was 2.1% (16/751). The histpathologic ROHM corresponding to each cytological diagnosis category were 27.3% for NHGUC, 32.7% for AUC, 74.7% for SHGUC, 96.6% for HGUC and 100.0% for NUM, respectively. ROHM of SHGUC was significantly higher than that of AUC group, and the difference between the two groups was statistically significant ( P＜0.001). ROHM of HGUC group was significantly higher than that of SHGUC group, and the difference was statistically significant ( P＜0.001). With SHGUC as the cut-off value, the sensitivity and specificity of cytological diagnosis of HGUC were 76.7% (165/215) and 85.7% (18/21), and with HGUC as the cut-off value, the sensitivity and specificity of cytological diagnosis of HGUC were 53.0% (114/215) and 100.0% (21/21), respectively. Conclusions:Urine cytology has high sensitivity and specificity in the diagnosis of HGUC. The malignant risk of TPS varies with different diagnosis category. The high malignant risk population in cancer hospital leads to the relatively high malignant proportion and ROHM in each diagnosis category. Urinary cytology TPS reporting system is helpful to clinical management and has good clinical application value.

Objective To explore the effects of standardized environmental enrichment(EE)on cognitive function and serum brain-derived neurotrophic factor(BDNF)levels in patients with post-stroke dementia.Methods A prospective study was conducted,including 80 patients with post-stroke dementia admitted to Department of Traditional Chinese Medicine Rehabilitation,910th Hospital of the Joint Logistics Support Force of Chinese PLA from January 2021 to May 2023.Patients were randomly divided into control group,cognitive training(COG)group,aerobic exercise training(AE)group and environmental enrichment(EE)group,with 20 cases in each group.All patients received routine treatment,with COG group receiving additional cognitive function training(30 minutes each time),AE group receiving additional aerobic exercise training(30 minutes each time),and EE group receiving both aerobic exercise and cognitive function training(15 minutes of aerobic exercise training and 15 minutes of cognitive training each time).The training was conducted once a day,5 days a week,for a total of 8 weeks.The patients'mini-mental state scale(MMSE),modified Barthel index(MBI),Hamilton depression scale(HAMD),stroke-specific quality of life(SS-QOL)score and serum levels of BDNF were assessed before treatment,at 4 weeks and 8 weeks of treatment,respectively.Results Before treatment,there were no significant differences in general information,MMSE,MBI,HAMD,SS-QOL scores,and serum levels of BDNF among the four groups(P＞0.05).After 4 and 8 weeks of treatment,the above indicators of the four groups were improved compared with those before treatment,with all differences being statistically significant(P＜0.05).Inter-group comparison showed that after 4 and 8 weeks of treatment,MMSE,MBI,SS-QOL scores,and serum BDNF levels in COG,AE and EE groups were significantly higher than those in control group,and HAMD scores were significantly lower than those in control group(P＜0.05).In addition,MMSE,MBI,SS-QOL scores and BDNF levels of group EE were better than those of other 3 groups,while HAMD scores were lower than those of other 3 groups,with all differences being statistically significant(P＜0.05).There was no significant difference in above outcome indicators between COG group and AE group after 4 and 8 weeks of treatment(P＞0.05).Conclusion Standardized enrichment environment can significantly enhance cognitive function,daily living abilities of post-stroke dementia patients,alleviate depression symptoms,and improve the quality of life,which may be related to the increase in serum BDNF levels.

Objective:To explore the effect of timely induction intervention on postpartum urination in primipara during vaginal delivery, so as to provide the evidence for preventing the occurrence of postpartum urinary retention and relieving the pain of primipara.Methods:This study adopted a randomized controlled trial design, and selected 400 cases of primipara who were hospitalized for vaginal delivery in the Obstetric Department of Dalian Women and Children's Medical Group Sports New Town Hospital from June 2021 to September 2022 as the study objects by convenience sampling method. They were divided into the intervention group and the control group with 200 cases each by random number table method, and the control group received routine postpartum care. Instruct active urination within 6 hours after delivery. The intervention received timely induction urination intervention. The general condition and bladder urine volume of the women in the intervention group were evaluated at 2, 4, 6 h after delivery, respectively, and personalized guidance was implemented, including the frequency of massage of the bottom of the uterus, the control of water intake, the selection of methods and timing of inducing urination, etc., and routine postpartum care was given when the women completed their first urination and had no complaints of discomfort. The first urination time, first urination volume, first bladder irritation during the first urination and the incidence of postpartum urinary retention in different periods were compared between the two groups.Results:The patients in the control group were (29.60 ± 3.20) years old, while the patients in the intervention group were (28.81 ± 3.42) years old. The first urination time in the intervention group was (6.89 ± 2.18) h, which was shorter than that in the control group (9.11 ± 3.86) h, and the difference was statistically significant ( t=-2.49, P<0.01). The first urination volume in the intervention group was (322.36 ± 120.15) ml, which was higher than that in the control group (262.93 ± 105.68) ml, and the difference was statistically significant ( t=3.39, P<0.05). The incidence of the first bladder irritation in the intervention group was 22.0%(44/200), which was lower than that in the control group 33.5%(67/200), and the difference was statistically significant ( χ2=6.60, P<0.05). The incidence of postpartum urinary retention within 24 h in the intervention group was 5.5%(11/200), which was lower than that in the control group 11.5%(23/200), and the difference was statistically significant ( χ2=4.63, P<0.05). The incidence of postpartum urinary retention within 1 week in the intervention group was 9.5%(19/200), which was lower than that in the control group 16.5%(33/200), and the difference was statistically significant ( χ2=4.33, P<0.05). There was no significant difference in the incidence of postpartum urinary retention within 24 to 72 h between the two groups ( P>0.05). Conclusions:Timely induction intervention can reduce the incidence of postpartum urinary retention, shorten the time of first urination, increase the volume of first urination and improve the comfort of first urination, which is worthy of clinical application.

Purpose: This study aims to evaluate the efficacy and safety of a new combination treatment of vinorelbine and pyrotinib in human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) and provide higher level evidence for clinical practice. Materials and Methods: This was a prospective, single-arm, phase 2 trial conducted at three institutions in China. Patients with HER2-positive MBC, who had previously been treated with trastuzumab plus a taxane or trastuzumab plus pertuzumab combined with a chemotherapeutic agent, were enrolled between March 2020 and December 2021. All patients received pyrotinib 400 mg orally once daily plus vinorelbine 25 mg/m2 intravenously or 60-80 mg/m2 orally on day 1 and day 8 of 21-day cycle. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival, and safety. Results: A total of 39 patients were enrolled. All patients had been pretreated with trastuzumab and 23.1% (n=9) of them had accepted trastuzumab plus pertuzumab. The median follow-up time was 16.3 months (95% confidence interval [CI], 5.3 to 27.2), and the median PFS was 6.4 months (95% CI, 4.0 to 8.8). The ORR was 43.6% (95% CI, 27.8% to 60.4%) and the DCR was 84.6% (95% CI, 69.5% to 94.1%). The median PFS of patients with versus without prior pertuzumab treatment was 4.6 and 8.3 months (p=0.017). The most common grade 3/4 adverse events were diarrhea (28.2%), neutrophil count decreased (15.4%), white blood cell count decreased (7.7%), vomiting (5.1%), and anemia (2.6%). Conclusion Pyrotinib plus vinorelbine showed promising efficacy and tolerable toxicity as second-line treatment in patients with HER2-positive MBC.

Colorectal cancer (CRC) is a prevalent malignant tumor often leading to liver metastasis and mortality. Despite some success with PD-1/PD-L1 immunotherapy, the response rate for colon cancer patients remains relatively low. This is closely related to the immunosuppressive tumor microenvironment mediated by tumor-associated macrophages (TAMs). Our previous work identified that a phosphoglycerate mutase 1 (PGAM1) allosteric inhibitor, HKB99, exerts a range of anti-tumor activities in lung cancer. Here, we found that upregulation of PGAM1 correlates with increased levels of M2-like tumor-associated macrophages (TAMs) in human colon cancer samples, particularly in liver metastatic tissues. HKB99 suppressed tumor growth and metastasis in cell culture and syngeneic tumor models. M2-polarization, induced by colon cancer cell co-culture, was reversed by HKB99. Conversely, the increased migration of colon cancer cells by M2-TAMs was remarkably restrained by HKB99. Notably, a decrease in TAM infiltration was required for the HKB99-mediated anti-tumor effect, along with an increase in CD8⁺ T cell infiltration. Moreover, HKB99 improved the efficacy of anti-PD-1 treatment in syngeneic tumors. Overall, this study highlights HKB99's inhibitory activity in TAM-mediated colon cancer progression. Targeting PGAM1 could lead to novel therapeutic strategies and enhance the effectiveness of existing immunotherapies for colon cancer.

To clarify the content characteristics of the main active components and mineral elements of Cynomorium songaricum under different habitat conditions, and further explore the relationship between the quality of C. songaricum and habitats, this study took C. songaricum from 25 different habitats in China as the research object, and measured the contents of 8 main active components and 12 mineral elements separately. Diversity analysis, correlation analysis, principal component analysis and cluster analysis were carried out. The results showed that the genetic diversity of total flavonoids, ursolic acid, ether extract, potassium(K), phosphorus(P) and zinc(Zn) in C. songaricum was high. The coefficient of variation of crude polysaccharide, ether extract, gallic acid, protocatechuic aldehyde, catechin, epicatechin, calcium(Ca), sodium(Na), magnesium(Mg), sulfur(S), iron(Fe), manganese(Mn), selenium(Se) and nickel(Ni) were all over 36%, indicating that the quality of C. songaricum was significantly affected by habitats. There were strong synergistic and weak antagonistic effects among the contents of the 8 active components, and complex antagonistic and synergistic effects among the contents of the 12 mineral elements. Principal component analysis revealed that crude polysaccharide, ursolic acid, catechin, epicatechin and total flavonoids could be used as the characteristic components to evaluate the quality of C. songaricum, and Na, copper(Cu), Mn and Ni were the characteristic elements to evaluate the quality of C. songaricum. In cluster ana-lysis, the second group with the main active components as cluster center had better quality in terms of the content of active substances, and the second group with the mineral elements as cluster center had higher utilization potential in the exploitation of mineral elements. This study could provide a basis for resource evaluation and breeding of excellent varieties of C. songaricum in different habitats, and provide a reference for cultivation and identification of C. songaricum.
Cynomorium ; Catechin ; Plant Breeding ; Selenium ; Ethers ; Ethyl Ethers ; Flavonoids ; Plant Extracts

In addition to the essential pharmacologi-cal effects of opioids,situational cues associated with drug addiction memory are key triggers for drug seeking.CircRNAs,an emerging hotspot regulator in crown genet-ics-play an important role in central nervous system-relat-ed diseases.However,the internal mediating mechanism of circRNA in the field of drug reward and addiction mem-ory remains unknown.Here,we trained mice on a condi-tional place preference(CPP)model and collected nucle-us accumbens(NAc)tissues from day 1(T0)and day 8(T1)for high-throughput RNA sequencing.qRT-PCR revealed that circTmeff-1 was highly expressed in the NAc core but not in the NAc shell,suggesting that it plays a role in addiction memory formation.Meanwhile,the reverse regulation of circTmeff-1 by adeno-associated viruses could both inhibit the formation of addiction mem-ory in the NAc core or shell.Subsequently,the GO and KEGG analyses indicated 21 that circTmeff-1 might regu-late the addiction memory via the MAPK and AMPK path-ways.These findings suggest that circTmeff-1 in NAc plays a crucial role in morphine-dependent memory for-mation.