1.Development of DUS Test Guidelines for New Pinellia ternata
Xinyao LI ; Mingxing WANG ; Bingbing LIAO ; Changjie CHEN ; Xiufu WAN ; Lanping GUO ; Yuhuan MIAO ; Dahui LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(10):225-233
Pinellia ternata, belonging to the Pinellia genus within the Araceae family, is a medicinal plant due to its tubers. There are severe issues with unclear germplasm and mixed varieties in its cultivation, necessitating urgent new variety protection efforts. The distinctness, uniformity, and stability (DUS) testing of the plant variety is the basis for protecting new plant varieties, and the DUS test guidelines are the technical basis for DUS testing. To develop the DUS test guidelines for P. ternata, agronomic traits of 229 germplasm of P. ternata were observed and measured during its two growth stages over the years, and each character was graded and described. A total of 38 traits were selected as the test traits of the DUS test guideline for P. ternata. There were three plant traits, 19 leaf traits, six flower traits, two fruit traits, two tuber traits, five bulbil traits, and one ploidy trait. These traits could be divided into 22 quality characters, 12 quantitative characters, and four pseudo-quantitative characters, as well as seven groups, including plants, leaves, flowers, fruit, tubers, bulbils, and ploidy. By searching for standard traits, 10 standard varieties were ultimately determined. Preparing these guidelines will have great significance for reviewing and protecting P. ternata varieties, safeguarding breeders' rights, and promoting the development of the P. ternata industry.
2.Advances in development of antiviral strategies against respiratory syncytial virus.
Ge YANG ; Guangyu JIANG ; Jiandong JIANG ; Yuhuan LI
Acta Pharmaceutica Sinica B 2025;15(4):1752-1772
Human respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in infants and young children, as well as an important cause of respiratory tract infections in immunocompromised patients and the elderly, which poses a significant economic and social burden worldwide. In recent years, substantial progress has been made in understanding the structure and function of RSV proteins and the interactions between RSV with host factors which is helpful to the discovery of new therapeutic targets and the development of novel interventions. Although two vaccines and two monoclonal antibodies for RSV prevention have been approved, the antiviral treatment remains an unmet clinical need. In this review, we summarize the structure, protein functional properties, and pathological mechanisms of RSV and the current status of RSV drug development. In addition, remaining challenges and innovative ideas for RSV prevention and treatment have also been highlighted.
3.Discovery and mechanism verification of first-in-class hydrophobic tagging-based degraders of HBV core protein.
Shujing XU ; Ya WANG ; Dazhou SHI ; Shuo WANG ; Lijun QIAO ; Ge YANG ; Yang ZHOU ; Xinyong LIU ; Shuo WU ; Yuhuan LI ; Peng ZHAN
Acta Pharmaceutica Sinica B 2025;15(4):2170-2196
Interfering hepatitis B virus (HBV) capsid assembly holds promise as a therapeutic approach for chronic hepatitis B (CHB). Novel anti-HBV agents are urgently needed to overcome drug resistance challenges, with targeted protein degradation (TPD) emerging as a hopeful strategy. Herein, we report the first degradation of HBV core protein (HBC), a multifunctional structural protein, using small-molecule degraders developed by hydrophobic tagging (HyT) technology. Structure-activity relationship (SAR) analysis identified compound HyT-S7, featuring an adamantyl group, exhibiting potent inhibitory activity (EC50 = 0.46 μmol/L, HepAD38 cells) and degradation ability (DC50 = 3.02 ± 0.54 μmol/L) in a dose- and time-dependent manner. Mechanistic studies demonstrated that the autophagy-lysosome pathway was a potential driver of HyT-S7-induced HBC degradation. Remarkably, HyT-S7 effectively degraded 11 drug-resistant mutants, including highly resistant strains P25G and T33N, to Phase III drug GLS4. Furthermore, cellular thermal shift assay, surface plasmon resonance assay, and molecular dynamics simulations revealed the precise mode of HyT-S7 binding to HBC with the adamantyl group potentially mimicking protein misfolding to facilitate HBC degradation. This first proof-of-concept study highlights the potential of HyT-mediated TPD in HBC as a promising avenue for discovering novel HBV and other antiviral agents with favorable drug resistance profiles.
4.Professor LIU Minru's Medication Rule in Treatment of Polycystic Ovary Syndrome (Intracellular Lipid Membrane Congestion Syndrome)
Xinbo HE ; Xiang HU ; Minru LIU ; Fuzhu LI ; Yuhuan HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(20):169-176
ObjectiveTo analyze and sum up the medication rule and the core prescription of Professor LIU Minru in the treatment of polycystic ovary syndrome (intracellular lipid membrane congestion syndrome)and explore the effect mechanism underlying the medication. MethodTwo platforms were used to carry out data mining to analyze the characteristics and rules of Professor LIU's prescriptions for the treatment of this disease. Network pharmacology was used to further clarify active ingredients in the core prescription,and a traditional Chinese medicine-active ingredient-target network was constructed,with the potential mechanism of action analyzed. ResultA total of 321 prescriptions were included in the medical records,involving 178 Chinese medicinals and 28 kinds of formula granules.The Chinese medicinals mainly act on the liver and kidney meridians, whose main tastes were sweetness,pungency,and bitterness and properties were mainly warm,mild,and slightly cold.Commonly used medicine pairs include Dioscoreae Rhizoma-Rehmanniae Radix Praeparata,Chuanxiong Rhizoma-Angelicae Sinensis Radix,Bupleuri Radix-Aurantii Fructus,and Gleditsiae Spina-Curcumae Rhizoma.The commonly used formulas are Xuefu Zhuyutang,Siwugang,Yangjing Zhongyutang,etc. The core prescription is composed of 12 Chinese medicinals such as angelica,white peony,saponaria thorn,and epimedium,containing 74 active ingredients,including quercetin,luteolin,kaempferol,fisetin,and β-sitosterol.A total of 37 key targets were found,involving phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt),mitogen-activated protein kinase (MAPK),Janus protein tyrosine kinase (JAK)/signal transduction and activator of transcription (STAT),and other signaling pathways. ConclusionThe pathogenesis of this disease is complex.Professor LIU adheres to the pathogenesis of "kidney deficiency as the root cause,and phlegm retention as the symptom". Under the guidance of the academic ideology of "kidney Qi as the root,and protecting Yin as the foundation" and "nurturing Yin to support Yang",she takes into account Yin and Yang in kidney tonic,replenishes and consolidates the essence and blood,and relieves manifestations by dissipating mass, activating blood, and regulating Qi. She has a rigorous thinking in formulating prescriptions. The core prescription has the characteristics of comprehensive regulation by multiple components at multiple targets in multiple pathways.
5.Diagnostic value of non-high-density lipoprotein cholesterol, ratio of triglyceride to high-density lipoprotein cholesterol and triglyceride glucose index for metabolic syndrome in adult women
Yi LIANG ; Zhongting YAN ; Xiaohong LI ; Fang WANG ; Yuhuan SANG ; Yuan YUAN ; Mei JU
Chinese Journal of Health Management 2024;18(1):35-41
Objective:To investigate the diagnostic value of non-high-density lipoprotein cholesterol (non-HDL-C),ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL-C), and triglyceride glucose index (TyG) on metabolic syndrome (MS) in adult women.Methods:This was a cross-sectional study. A total of 24 410 adult women who received health examination in health management center of the Affiliated Hospital of Southwest Medical University were selected from January 2019 to December 2021 as subjects. The subjects′ basic information, physical examination results, and laboratory examination data were collected retrospectively. The relationship between non-HDL-C, TG/HDL-C, TyG, and MS in adult women were examined using multivariate logistic regression analysis. The receiver operating characteristic (ROC) curves were constructed and the area under the curve (AUC) were calculated to evaluate the diagnostic value of each indicator for MS in adult women.Results:Among 24 410 adult females, 800 (3.3%) were found to have MS. After adjusting for age, body mass index, waist circumference, hip circumference, systolic blood pressure, diastolic blood pressure, blood uric acid, history of hypertension, history of diabetes, fatty liver, non HDL-C ( OR=1.608), TG/HDL-C ( OR=1.311), TyG ( OR=13.288) were all risk factors for MS in adult women. non-HDL-C, TG/HDL-C, and TyG, as well as their combined AUC of ROC, were 0.795 (95% CI: 0.742-0.776), 0.909 (95% CI: 0.902-0.917), 0.942 (95% CI: 0.937-0.948), and 0.944 (95% CI: 0.937-0.950), respectively. TyG had the highest diagnostic value for MS in adult women among the three indicators, the optimal cutoff value for TyG was 8.237, with a sensitivity of 93.5% and a specificity of 85.5%. Conclusion:non-HDL-C, TG/HDL-C, TyG, as well as their combination, all demonstrate good diagnostic value for MS in adult women.
6.Diagnostic value of plasma SPINK4 expression in colorectal adenocarcinoma and progressive adenoma
Longmei ZHOU ; Ping LI ; Yuhuan SHANG ; Yanling WANG ; Chunying YIN ; Dan LI ; Peiyuan HE
Chongqing Medicine 2024;53(1):50-54
Objective To investigate the clinical diagnostic value of plasma serine protease inhibitor Ka-zal-type 4(SPINK4)expression in colorectal adenocarcinoma(CRC)and progressive adenoma(AA).Methods A total of 62 patients with CRC(CRC group)and 15 patients with AA(AA group)diagnosed by colonoscopy and pathological examination in this hospital from June 2020 to December 2021 were selected,and 22 healthy people undergoing physical examination during the same period were selected as the HC group.The expression of SPINK4 in plasma was detected by ELISA,and the expression of CEA in plasma was detected by electrochemiluminescence,and the correlation was analyzed.The diagnostic efficiency was analyzed by re-ceiver operating characteristic(ROC)curve,and the expression of p53 in CRC tissues was detected by immu-nohistochemistry.Results The expression of plasma SPINK4 in the CRC group and AA group was lower than that in the HC group(Z=3.72,-0.41,P<0.05),and the expression of CEA in the CRC group was higher than that in the HC group(Z=-3.63,P<0.05).The area under the curve(AUC),accuracy,sensi-tivity and specificity of SPINK4 combined with CEA in the diagnosis of CRC and AA were higher than those of SPINK4 and CEA alone.The positive rate of mutant type p53 in SPINK4 low expression group and CEA high ex-pression group was significantly increased in CRC patients(72.55%,75.00%,P<0.05).Conclusion The expression of plasma SPINK4 is decreased in CRC and AA,and the combined detection of SPINK4 and CEA has a good di-agnostic efficiency in CRC and AA.
7.Analysis of mini-CEX Scores and influencing factors after teaching"fundamentals of nursing"in the elderly service management program
Aili CEN ; Liping HUANG ; Jinyan ZENG ; Yuhuan DU ; Xin YAO ; Li LU
Modern Hospital 2024;24(10):1614-1617
Objective To investigate the current status of mini-CEX scores among students in the Elderly Service Man-agement program after completing the"Fundamentals of Nursing"course and analyze the influencing factors.Methods A total of 99 students from the Elderly Service Management program at the Wuming campus of Guangxi Medical University were selected as the study subjects.Assessment tools included a general information questionnaire,the Chinese version of the Mini Clinical E-valuation Exercise(mini-CEX),the Self-Rating Scale of Self-Directed Learning(SRSSDL),and a self-learning ability assess-ment scale.Stepwise linear regression analysis was employed to explore the factors affecting mini-CEX scores.Results The total mini-CEX score for the 99 students was 49.00(44.00,55.00).Stepwise linear regression analysis revealed that being a student leader,SRSSDL scores,self-learning ability,and teaching model were significant factors(P<0.05),explaining 56.8%of the total variance.Conclusion The clinical comprehensive ability of students in the Elderly Service Management program requires enhancement,influenced by multiple factors including teaching model,self-learning ability,and self-directed learning capacity.
8.Establishment of a risk model based on immunogenic cell death-related genes and its value in predicting the prognosis and tumor microenvironment characteristics of hepatocellular carcinoma
Jun LIU ; Ling WANG ; Yuhuan JIANG ; Jingzhi WANG ; Huiming LI
Journal of Clinical Hepatology 2024;40(12):2473-2483
ObjectiveTo identify immunogenic cell death (ICD)-related genes in hepatocellular carcinoma (HCC), and to establish a scoring model based on these genes for predicting the prognosis and tumor microenvironment characteristics of HCC. MethodsThe Cancer Genome Atlas database was used to obtain HCC datasets, and heatmaps were used to display the expression of 57 ICD-related genes in HCC. A cluster analysis was conducted based on the expression of ICD-related genes, and two ICD subtypes (low and high ICD expression groups) were analyzed in terms of gene ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, somatic mutation, and immune cell infiltration. The LASSO Cox regression risk model was constructed to evaluate its clinical application value, and a nomogram model was established to predict the 1-, 3-, and 5-year survival rates of patients. In addition, qRT-PCR was used to validate the expression levels of key genes in the model. The independent-samples t test was used for comparison between two groups, and the univariate and multivariate Cox regression analyses were used to determine prognostic factors among clinicopathological features. The Kaplan-Meier survival curve was used for prognostic analysis, and the Spearman rank correlation test was used for correlation analysis. ResultsThe low ICD expression group had a poorer prognosis, while the high ICD expression group had relatively favorable clinical outcomes (P=0.004). Further analysis showed that the high ICD expression group was associated with an immune-active microenvironment, and the genes were mainly enriched in immune-related pathways such as immunoglobulin receptor binding, hematopoietic cell lineage, and B cell receptor. The results of somatic mutation analysis showed that the high ICD expression group had higher expression levels of CD274, CTLA4, HAVCR2, TIGIT, PDCD1, and PDCD1LG2 (all P<0.05). A risk prediction model was established using 8 ICD-related genes, i.e., HSP90AA1, ATG5, BAX, PPIA, HSPA4, TLR2, TREM1, and LY96, and this model showed a good predictive value across different clinical characteristics. The univariate and multivariate Cox regression analyses showed that age and risk score were independent prognostic factors for overall survival in the training set (both P<0.05). The results of qRT-PCR showed that the relative expression levels of HSPA4 and REM1 in HCC tumor samples were significantly higher than those in adjacent tissue samples (both P<0.001). For the patients with an increase in ICD risk score, the ICD risk score was negatively correlated with γδT cells (r=-0.29, P<0.05), plasma cells (r=-0.3, P<0.05), and CD8+T lymphocytes (r=-0.37, P<0.05) and was positively correlated with memory B cells (r=0.38, P<0.05), resting dendritic cells (r=0.47, P<0.05), and M0 macrophages (r=0.49, P<0.05). ConclusionThis study identifies the ICD-related genes that are associated with the prognosis of HCC, which provides insights into the immune characteristics of different ICD expression profiles. The risk model and the nomogram model established in this study have a significant value for predicting the prognosis of HCC patients and guiding immunotherapy for HCC patients.
9.Secondary metabolites of mulberry leaves exert anti-lung cancer activity through regulating the PD-L1/PD-1 signaling pathway
Ye GUIQIN ; Sun XIN ; Li JIUZHOU ; Mai YUANYUAN ; Gao RUILAN ; Zhang JIANBIN
Journal of Pharmaceutical Analysis 2024;14(6):914-925
Lung cancer ranks the top of malignancies that cause cancer-related deaths worldwide.The leaves of Morus alba L are traditional Chinese medicine widely applied in respiratory diseases.Our previous work has demonstrated the anti-lung cancer effect of secondary metabolites of mulberry leaf,but their mechanism of action has still not fully elucidated.We synthesized Moracin N(MAN)-Probe conjugated with alkyne to label lung cancer cells and identified protein targets by chemical proteomic analysis.MAN and its probe exerted similar growth-inhibitory effect on human lung cancer cells.Chemical proteomic results showed that MAN targeted the programmed death ligand 1(PD-L1)checkpoint pathway and T cell receptor(TCR)signaling pathway,indicating its immune-regulatory function.Cell-free surface plasmon resonance(SPR)results showed the direct interaction of MAN with PD-L1 protein.Molecular docking analysis demonstrated that MAN bound to E158 residue of PD-L1 protein.MAN downregulated the expression levels of PD-L1 in a time-and dose-dependent manner and disrupted the PD-L1/programmed death 1(PD-1)binding,including other secondary metabolites of mulberry leaves Guangsangon E(GSE)and Chalcomoracin(CMR).Human peripheral blood mononuclear cells(PBMCs)co-cultured with MAN-treated A549 cells,resulting in the increase of CD8+GZMB+T cells and the decrease of CD8+PD-1+T cells.It suggested that MAN exerts anti-cancer effect through blocking the PD-L1/PD-1 signaling.In vivo,MAN combined with anti-PD-1 antibody significantly inhibited lung cancer development and metastasis,indicating their synergistic effect.Taken together,secondary metabolites of mulberry leaves target the PD-L1/PD-1 signaling,enhance T cell-mediated immunity and inhibit the tumorigenesis of lung cancer.Their modulatory effect on tumor microenvironment makes them able to enhance the therapeutic efficacy of immune checkpoint inhibitors in lung cancer.
10.Characteristics of genioglossus neuromuscular activity in patients with obstructive sleep apnea during drug-induced sleep
Yingqian ZHOU ; Jinkun XU ; Guoping YIN ; Xin CAO ; Jingjing LI ; Yuhuan ZHANG ; Jingying YE
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2023;58(10):951-958
Objective:To analyze genioglossus (GG) activation responses to the negative pressure of upper airway cavity during awake and different sleep stages in patients with different obstructive sleep apnea (OSA) graduation.Methods:This prospective cohort study started from August 2019 to January 2021, recruited 42 male OSA patients aged from 21 to 59 (38.77±8.42) years. After completing whole night polysomnography (PSG) and upper airway CT, each subject underwent drug-induced sleep with simultaneous monitoring of genioglossal electromyography (GGEMG) and pressure of epiglottis (P epi). Subjects were divided into three groups of mild OSA(7 males), moderate OSA(12 males), and severe OSA(23 males). The differences in upper airway CT measurements, parameters of GGEMG and P epi during awake and induced sleep were compared. Statistical analysis was conducted by SPSS 21.0. Results:There was no significant difference in the GGEMG parameters between the mild and moderate groups. In wakefulness, the peak phasic GGEMG of the severe group was higher than the mild group ( t=1.249, P=0.025), with no statistically difference in the corresponding P epi. In the sleep onset, the GGEMG parameters and P epi in severe group were higher than the other two groups. Linear regression analysis of the maximum GGEMG and maximum P epi at the end of obstructive apnea (OA) in all moderate plus severe patients ( n=35) was shown nonlinear correlation ( r=0.28, P=0.694). The airway length of the glossopharyngeal cavity was linearly correlated with the maximum P epi of OA ( r=0.468, R2=0.219, P=0.005). Conclusions:The individual difference of GG activation in OSA patients is related to the severity of the disease (frequency of respiratory events) and negative pressure stimulation. In moderate and severe OSA patients, GG activity is not in harmony with the corresponding negative pressure stimulation, which may be one of the mechanisms leading to the aggravation of OSA.

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