1.Arginine Metabolic Disorder in Heart Failure Rats: Analysis Based on Targeted Metabolomics and Bioinformatics
Zeyu LI ; Xiaoqing WANG ; Zhengyu FANG ; Yurou ZHAO ; He XIAO ; Penghaobang LIU ; Haiming ZHANG ; Chunyan LIU ; Yanhong HU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):229-237
ObjectiveThis study systematically analyzed the arginine metabolic dysregulation in the rat model of heart failure (HF), providing a modern scientific basis for elucidating the pathogenesis of HF and offering new insights for the prevention and treatment of HF with traditional Chinese medicine (TCM). MethodsA thoracotomy was performed to ligate the left anterior descending coronary artery of rats, which induced acute myocardial ischemia and thus led to the development of post-myocardial infarction heart failure. The rats were divided into a sham surgery group and a model group, with eight rats in each group. Serum targeted metabolomics analysis was performed using ultra-performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-TQ-S), and the spatial distribution of metabolites in cardiac tissue was observed using airflow-assisted desorption electrospray ionizationmass spectrometry imaging (AFADESI-MSI). Targets associated with HF and arginine metabolism were screened from databases including GeneCards and the Gene Expression Omnibus (GEO), a protein-protein interaction (PPI) network was constructed, and enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) was performed. Finally, molecular docking was conducted to verify the binding between core metabolic components and key targets, and potential TCMs were predicted based on the core pathways and targets. ResultsCompared with the sham surgery group, the levels of arginine and citrulline in the serum of model rats were significantly decreased (P<0.01), while those of proline, ornithine, creatine, creatinine and glutamate were significantly increased (P<0.05, P<0.01). Cardiac mass spectrometry imaging showed a decreased abundance of arginine in the local myocardial tissue. Bioinformatics analysis identified 24 core functional targets, such as the angiotensin-converting enzyme (ACE), neuronal nitric oxide synthase (NOS1), 5-hydroxytryptamine receptor 2A (HTR2A), and epidermal growth factor receptor (EGFR), and enrichment analysis indicated that these targets were significantly involved in the calcium signaling pathway, neuroactive ligand-receptor interactions, and phosphatidylinositol signaling pathway. Molecular docking confirmed strong binding activities between arginine, citrulline and HTR2A, as well as between creatine, creatinine and EGFR. Based on pathway-target prediction, potential TCM interventions, such as ginseng and magnolia, were identified. ConclusionThis study revealed characteristic arginine metabolic disorder in HF, and the core targets of HF were closely associated with the phosphatidylinositol signaling pathway. It provides a modern biological interpretation of the pathogenesis of HF in TCM from the perspectives of metabolites and signaling pathways, and offers valuable insights for targeted therapy of HF and the development of TCM.
2.Arginine Metabolic Disorder in Heart Failure Rats: Analysis Based on Targeted Metabolomics and Bioinformatics
Zeyu LI ; Xiaoqing WANG ; Zhengyu FANG ; Yurou ZHAO ; He XIAO ; Penghaobang LIU ; Haiming ZHANG ; Chunyan LIU ; Yanhong HU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):229-237
ObjectiveThis study systematically analyzed the arginine metabolic dysregulation in the rat model of heart failure (HF), providing a modern scientific basis for elucidating the pathogenesis of HF and offering new insights for the prevention and treatment of HF with traditional Chinese medicine (TCM). MethodsA thoracotomy was performed to ligate the left anterior descending coronary artery of rats, which induced acute myocardial ischemia and thus led to the development of post-myocardial infarction heart failure. The rats were divided into a sham surgery group and a model group, with eight rats in each group. Serum targeted metabolomics analysis was performed using ultra-performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-TQ-S), and the spatial distribution of metabolites in cardiac tissue was observed using airflow-assisted desorption electrospray ionizationmass spectrometry imaging (AFADESI-MSI). Targets associated with HF and arginine metabolism were screened from databases including GeneCards and the Gene Expression Omnibus (GEO), a protein-protein interaction (PPI) network was constructed, and enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) was performed. Finally, molecular docking was conducted to verify the binding between core metabolic components and key targets, and potential TCMs were predicted based on the core pathways and targets. ResultsCompared with the sham surgery group, the levels of arginine and citrulline in the serum of model rats were significantly decreased (P<0.01), while those of proline, ornithine, creatine, creatinine and glutamate were significantly increased (P<0.05, P<0.01). Cardiac mass spectrometry imaging showed a decreased abundance of arginine in the local myocardial tissue. Bioinformatics analysis identified 24 core functional targets, such as the angiotensin-converting enzyme (ACE), neuronal nitric oxide synthase (NOS1), 5-hydroxytryptamine receptor 2A (HTR2A), and epidermal growth factor receptor (EGFR), and enrichment analysis indicated that these targets were significantly involved in the calcium signaling pathway, neuroactive ligand-receptor interactions, and phosphatidylinositol signaling pathway. Molecular docking confirmed strong binding activities between arginine, citrulline and HTR2A, as well as between creatine, creatinine and EGFR. Based on pathway-target prediction, potential TCM interventions, such as ginseng and magnolia, were identified. ConclusionThis study revealed characteristic arginine metabolic disorder in HF, and the core targets of HF were closely associated with the phosphatidylinositol signaling pathway. It provides a modern biological interpretation of the pathogenesis of HF in TCM from the perspectives of metabolites and signaling pathways, and offers valuable insights for targeted therapy of HF and the development of TCM.
3.Effect and Mechanism of Icariin on Improving Spermatogenesis in Exercise-induced Fatigue Model Mice Through Regucalcin
Kunyang TANG ; Min XIAO ; Xiaocui JIANG ; Xiaoxue TAO ; Yue ZOU ; Chunchun ZHAO ; Zhipeng FANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):117-127
ObjectiveThis paper aims to investigate the effects of icariin on spermatogenesis in mice with exercise-induced fatigue and explore the underlying mechanisms. MethodsICR male mice were screened by swimming and randomly divided into normal group, model group, vitamin C group, icariin groups with low, medium, and high doses, and medium-dose icariin+N-nitro-L-arginine methyl ester (L-NAME) group, with 10 mice per group. Except for the normal group, all the other groups underwent weighted swimming training to establish an exercise-induced fatigue model. No gavage was administered during the first two weeks of the weighted training. From week three to four, the icariin groups with low, medium, and high doses received 0.03, 0.06, and 0.12 g·kg-1 icariin via gavage, respectively. The vitamin C group received 0.2 g·kg-1 vitamin C. The L-NAME group received 0.06 g·kg-1 icariin and 0.01 g·kg-1 L-NAME via intraperitoneal injection. The normal and model groups received equivalent physiological saline. After the experiment, body weight and the last exhaustive swimming time were recorded. Blood urea nitrogen (BUN), lactate (LA), lactate dehydrogenase (LDH), malondialdehyde (MDA), testicular testosterone (T), testicular Ca2+/Mg2+-adenosine triphosphatase (ATPase) (micro-assay), and the levels of testicular cyclic guanosine monophosphate (cGMP) were measured by using kits. Sperm CD46 levels were detected by flow cytometry. Testicular seminiferous tubules were observed via hematoxylin-eosin (HE) staining, and the testicular morphometric score (TMS) was used to evaluate the spermatogenic function. Protein expression of regucalcin (RGN, SMP30), cGMP-dependent protein kinase 1 (PKG), and cGMP-dependent protein kinase anchoring protein (GKAP1) was detected by Western blot. Testicular regucalcin expression was examined by immunofluorescence (IF). The epididymal sperm quality of mice was observed under a microscope. Fluorescence-stained sections of stimulated by retinoic acid gene 8 (STRA8), synaptonemal complex protein 3 (SCP3), and transition protein 1(TNP1) in testicular seminiferous tubules were assessed by immunohistochemistry (IHC). ResultsCompared with the normal group, the model group showed decreased body weight and exhaustive swimming time (P<0.01), significantly increased fatigue markers (LA, LDH, and BUN) and lipid peroxidation product MDA (P<0.01), reduced testicular RGN, PKG, GKAP1, testosterone, Ca2+/Mg2+-ATPase, and cGMP levels (P<0.01), decreased sperm motility, sperm count, and TMS scores, and downregulated the expression of STRA8, SCP3, and TNP1. Compared with the model group, the icariin group with high dose exhibited increased exhaustive swimming time (P<0.01), reduced LA, LDH, BUN, and MDA levels (P<0.01), elevated superoxide dismutase (SOD) (P<0.01), upregulated testicular RGN, PKG, GKAP1, testosterone, Ca2+/Mg2+-ATPase, and cGMP levels (P<0.01), improved sperm motility, sperm count, and TMS scores, and enhanced STRA8, SCP3, and TNP1 expression. Compared with the L-NAME group, the icariin group with medium dose showed increased expression of STRA8, SCP3, and TNP1 in the testicular tissue (P<0.01) and elevated cGMP and GKAP1 levels (P<0.01). ConclusionExercise-induced fatigue reduces the expression of RGN and cGMP/PKG/GKAP1 in mice, thereby causing abnormal spermatogenesis and impairing reproductive function in mice. Icariin ameliorates spermatogenic dysfunction in exercise-induced fatigue mice by promoting the expression of RGN and cGMP/PKG/GKAP1, thereby mitigating the damage of exercise-induced fatigue to the reproductive system.
4.Effect and Mechanism of Icariin on Improving Spermatogenesis in Exercise-induced Fatigue Model Mice Through Regucalcin
Kunyang TANG ; Min XIAO ; Xiaocui JIANG ; Xiaoxue TAO ; Yue ZOU ; Chunchun ZHAO ; Zhipeng FANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):117-127
ObjectiveThis paper aims to investigate the effects of icariin on spermatogenesis in mice with exercise-induced fatigue and explore the underlying mechanisms. MethodsICR male mice were screened by swimming and randomly divided into normal group, model group, vitamin C group, icariin groups with low, medium, and high doses, and medium-dose icariin+N-nitro-L-arginine methyl ester (L-NAME) group, with 10 mice per group. Except for the normal group, all the other groups underwent weighted swimming training to establish an exercise-induced fatigue model. No gavage was administered during the first two weeks of the weighted training. From week three to four, the icariin groups with low, medium, and high doses received 0.03, 0.06, and 0.12 g·kg-1 icariin via gavage, respectively. The vitamin C group received 0.2 g·kg-1 vitamin C. The L-NAME group received 0.06 g·kg-1 icariin and 0.01 g·kg-1 L-NAME via intraperitoneal injection. The normal and model groups received equivalent physiological saline. After the experiment, body weight and the last exhaustive swimming time were recorded. Blood urea nitrogen (BUN), lactate (LA), lactate dehydrogenase (LDH), malondialdehyde (MDA), testicular testosterone (T), testicular Ca2+/Mg2+-adenosine triphosphatase (ATPase) (micro-assay), and the levels of testicular cyclic guanosine monophosphate (cGMP) were measured by using kits. Sperm CD46 levels were detected by flow cytometry. Testicular seminiferous tubules were observed via hematoxylin-eosin (HE) staining, and the testicular morphometric score (TMS) was used to evaluate the spermatogenic function. Protein expression of regucalcin (RGN, SMP30), cGMP-dependent protein kinase 1 (PKG), and cGMP-dependent protein kinase anchoring protein (GKAP1) was detected by Western blot. Testicular regucalcin expression was examined by immunofluorescence (IF). The epididymal sperm quality of mice was observed under a microscope. Fluorescence-stained sections of stimulated by retinoic acid gene 8 (STRA8), synaptonemal complex protein 3 (SCP3), and transition protein 1(TNP1) in testicular seminiferous tubules were assessed by immunohistochemistry (IHC). ResultsCompared with the normal group, the model group showed decreased body weight and exhaustive swimming time (P<0.01), significantly increased fatigue markers (LA, LDH, and BUN) and lipid peroxidation product MDA (P<0.01), reduced testicular RGN, PKG, GKAP1, testosterone, Ca2+/Mg2+-ATPase, and cGMP levels (P<0.01), decreased sperm motility, sperm count, and TMS scores, and downregulated the expression of STRA8, SCP3, and TNP1. Compared with the model group, the icariin group with high dose exhibited increased exhaustive swimming time (P<0.01), reduced LA, LDH, BUN, and MDA levels (P<0.01), elevated superoxide dismutase (SOD) (P<0.01), upregulated testicular RGN, PKG, GKAP1, testosterone, Ca2+/Mg2+-ATPase, and cGMP levels (P<0.01), improved sperm motility, sperm count, and TMS scores, and enhanced STRA8, SCP3, and TNP1 expression. Compared with the L-NAME group, the icariin group with medium dose showed increased expression of STRA8, SCP3, and TNP1 in the testicular tissue (P<0.01) and elevated cGMP and GKAP1 levels (P<0.01). ConclusionExercise-induced fatigue reduces the expression of RGN and cGMP/PKG/GKAP1 in mice, thereby causing abnormal spermatogenesis and impairing reproductive function in mice. Icariin ameliorates spermatogenic dysfunction in exercise-induced fatigue mice by promoting the expression of RGN and cGMP/PKG/GKAP1, thereby mitigating the damage of exercise-induced fatigue to the reproductive system.
5.Differences in deltamethrin resistance and kdr gene mutation in Culex tritaeniorhynchus population in and outside the Yellow Sea wetland
Xiao-er ZHANG ; Zhi-ming WU ; Ye TIAN ; Qian CUI ; Yu-qian JI ; Huan WANG ; Shu-juan YANG ; Yi-chao ZHAO ; Yu WANG ; Hua-yu YIN ; Yu DING ; Guo-jin YAN ; Min-sen ZHAO ; Shou-gang ZHANG ; Bing-dong SONG ; Hong-na CHEN ; Jian GAO ; Wei-fang YANG ; Yu-fu ZHANG ; Hui LIU ; Hong-liang CHU
Acta Parasitologica et Medica Entomologica Sinica 2026;33(2):101-107
Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.
6.MTAP Orchestrates Stemenss and 5-Fluorouracil Resistance in Liver Cancer via PRMT5/SOX2 Signaling
Yu-Bo ZHANG ; Zhao-Xiong FANG ; Yun LI ; Jie DONG ; Xiao-Peng HONG ; Hui LUO
Progress in Biochemistry and Biophysics 2026;53(10):2797-2807
ObjectiveMethylthioadenosine phosphorylase (MTAP) is found to be frequently deleted in malignant cancers, but the role of MTAP underlying metastasis and stemness of liver cancer remains far from clear. 5-fluorouracil (5-Fu) is clinically used in treating advanced liver cancer, however, chemoresistance is one of the major barriers impeding its efficacy. Liver cancer stem cells are considered to be the reservoir for tumor progression and chemoresistance. This study aims to explore the role of MTAP in regulating stemness and chemoresistance of 5-Fu in liver cancer. It is designed to elucidate the molecular mechanisms underlying MTAP-manipulated stemness. How MTAP influences metastasis and chemoresistance against 5-Fu in liver cancer is also elaborated. MethodsThe correlation of MTAP expression with stemness marker CD133 was evaluated by flow cytometry. Colony formation assays were conducted to analyze the tumorigenic ability. Western blot assays were applied to delineate the molecular mechanisms underlying MTAP-regulated stemness. Trans-well assays were conducted to analyze the metastatic potential of liver cancer cells.In vivo experiments were performed using subcutaneous xenograft and lung metastasis model on nude mice. Tumor size and weight were analyzed upon 5-Fu treatment. Metastatic nodules on lungs were evaluated. Immunohistochemical and TUNNEL assays were performed on slides obtained from tumor tissues. ResultsMTAP overexpression inhibited expression of CD133 and colony formation, which is further ablated by MTAP inhibitor. MTAP deprivation augmented stemness and colony formation, which is reversed by protein arginine methyltransferase 5 (PRMT5) overexpression but not its catalytically inactive counterparts. Critically, SRY-box transcription factor 2 (SOX2) was found to be a downstream regulator of MTAP/PRMT5, leading to stemness of liver cancer cells. MTAP overexpression suppressed SOX2 expression, while MTAP inhibition augmented expression of SOX2. Critically, MTAP overexpression inhibited migration and invasion of liver cancer cells. In vivo experiments in animal model found that MTAP deprivation promotes tumor growth and metastatic nodules of liver cancer. Additionally, MTAP overexpression inhibits tumor growth. Moreover, MTAP deprivation contributes to chemoresistance shown by increased tumor size and weight treated by 5-Fu. In contrast, MTAP overexpression led to further decline in tumor size and weight elicited by 5-Fu treatment. Accordingly, SOX2 was inhibited in tumor tissues after MTAP overexpression. Marker of proliferation Ki67 (Ki67) expression was dampened while apoptosis was found in MTAP-overexpressed tumor tissues. ConclusionIn this study, plethora of experimental studies collectively demonstrated that MTAP deprivation enhances stemness of liver cancer by regulating SOX2, exerting anti-cancer and chemoresistant role against 5-Fu in liver cancer. It is also worth noting that MTAP inhibition promoted metastasis of liver cancer. MTAP overexpression augmented tumor shrinking elicited by 5-Fu and SOX2 was involved in this process. These results concluded that MTAP/PRMT5/SOX2 signaling axis was involved in regulating stemness and chemoresistance of liver cancer. These findings help to exploit novel therapies by targeting stemness in MTAP-depleted liver cancer. It shed novel light on unveiling MTAP-regulated stemness in antagonizing 5-Fu treatment in liver cancer. It also adds mounting evidence to the theoretical basis for accomplishing personalized chemotherapy of liver cancer patients by targeting MTAP or its downstream PRMT5/SOX2.
7.Effect of chromosome-instability-associated gene GALNT7 on proliferation and apoptosis of HCT116 colon cancer cells
Xiao Fang ; Wei Zhao ; Wenying Yu ; Lingjie Pei ; Wenxuan Qian ; Ya Zhao
Acta Universitatis Medicinalis Anhui 2025;60(1):96-101
Objective :
To investigate the effect of chromosome instability(CIN) associated gene polypeptide N-acetylgalactosaminyltransferase 7(GALNT7) on proliferation and apoptosis of HCT116 colon cancer cells.
Methods :
The HCT116 cell line withGALNT7knockdown was constructed by lentiviral infection. The correlation betweenGALNT7and CIN was verified by chromosome spread assay. The effect ofGALNT7on cell proliferation was detected by live cell counting, and the effect ofGALNT7on cell cycle distribution was detected by flow cytometry and Western blot. Caspase-3 activity and Western blot assays were used to detect the effect ofGALNT7on apoptosis.
Results :
HCT116 cells showed a slower proliferation rate upon knocking down ofGALNT7, and exhibited a more scattered karyotype distribution and a phenotype of increased degree of CIN. Inhibition ofGALNT7in HCT116 cells resulted in cell cycle arrest, upregulation of P21 and downregulation of CDK6 protein levels, as well as increased levels of Caspase-3 activity, cleaved PARP1 and PUMA protein expression, and decreased levels of BCL-2 protein expression.
Conclusion
TheGALNT7gene may promote proliferation and inhibit apoptosis of HCT116 colon cancer cells through the suppression of CIN generation.
8.Value of different noninvasive diagnostic models in the diagnosis of esophageal and gastric varices with significant portal hypertension in compensated hepatitis B cirrhosis
Cheng LIU ; Jiayi ZENG ; Mengbing FANG ; Zhiheng CHEN ; Bei GUI ; Fengming ZHAO ; Jingkai YUAN ; Chaozhen ZHANG ; Meijie SHI ; Yubao XIE ; Xiaoling CHI ; Huanming XIAO
Journal of Clinical Hepatology 2025;41(2):263-268
ObjectiveTo investigate the value of different noninvasive diagnostic models in the diagnosis of esophageal and gastric varices since there is a high risk of esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension, and to provide a basis for the early diagnosis of esophageal and gastric varices. MethodsA total of 108 patients with significant portal hypertension due to compensated hepatitis B cirrhosis who attended Guangdong Provincial Hospital of Traditional Chinese Medicine from November 2017 to November 2023 were enrolled, and according to the presence or absence of esophageal and gastric varices under gastroscopy, they were divided into esophageal and gastric varices group (GOV group) and non-esophageal and gastric varices group (NGOV group). Related data were collected, including age, sex, imaging findings, and laboratory markers. The chi-square test was used for comparison of categorical data between groups; the least significant difference t-test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups. The receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic value of five scoring models, i.e., fibrosis-4 (FIB-4), LOK index, LPRI, aspartate aminotransferase-to-platelet ratio index (APRI), and aspartate aminotransferase/alanine aminotransferase ratio (AAR). The binary logistic regression method was used to establish a combined model, and the area under the ROC curve (AUC) was compared between the combined model and each scoring model used alone. The Delong test was used to compare the AUC value between any two noninvasive diagnostic models. ResultsThere were 55 patients in the GOV group and 53 patients in the NGOV group. Compared with the NGOV group, the GOV group had a significantly higher age (52.64±1.44 years vs 47.96±1.68 years, t=0.453, P<0.05) and significantly lower levels of alanine aminotransferase [42.00 (24.00 — 17.00) U/L vs 82.00 (46.00 — 271.00) U/L, Z=-3.065, P<0.05], aspartate aminotransferase [44.00 (32.00 — 96.00) U/L vs 62.00 (42.50 — 154.50) U/L,Z=-2.351, P<0.05], and platelet count [100.00 (69.00 — 120.00)×109/L vs 119.00 (108.50 — 140.50)×109/L, Z=-3.667, P<0.05]. The ROC curve analysis showed that FIB-4, LOK index, LPRI, and AAR used alone had an accuracy of 0.667, 0.681, 0.730, and 0.639, respectively, in the diagnosis of esophageal and gastric varices (all P<0.05), and the positive diagnostic rates of GOV were 69.97%, 65.28%, 67.33%, and 58.86%, respectively, with no significant differences in AUC values (all P>0.05), while APRI used alone had no diagnostic value (P>0.05). A combined model (LAF) was established based on the binary logistic regression analysis and had an AUC of 0.805 and a positive diagnostic rate of GOV of 75.80%, with a significantly higher AUC than FIB-4, LOK index, LPRI, and AAR used alone (Z=-2.773,-2.479,-2.206, and-2.672, all P<0.05). ConclusionFIB-4, LOK index, LPRI, and AAR have a similar diagnostic value for esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension, and APRI alone has no diagnostic value. The combined model LAF had the best diagnostic efficacy, which provides a certain reference for clinical promotion and application.
9.Design, synthesis and biological evaluation of a novel class of indazole-containing compounds with potent anti-influenza activities targeting the PA-PB1 interface.
Yun-Sang TANG ; Chao ZHANG ; Jing XU ; Haibo ZHANG ; Zhe JIN ; Mengjie XIAO ; Nuermila YILIYAER ; Er-Fang HUANG ; Xin ZHAO ; Chun HU ; Pang-Chui SHAW
Acta Pharmaceutica Sinica B 2025;15(6):3163-3180
The PA-PB1 interface of the influenza polymerase is an attractive site for antiviral drug design. In this study, we designed and synthesized a mini-library of indazole-containing compounds based on rational structure-based design to target the PB1-binding interface on PA. Biological evaluation of these compounds through a viral yield reduction assay revealed that compounds 27 and 31 both had a low micromolar range of the half maximal effective concentration (EC50) values against A/WSN/33 (H1N1) (8.03 μmol/L for 27; 14.6 μmol/L for 31), while the most potent candidate 24 had an EC50 value of 690 nM. Compound 24 was effective against different influenza strains including a pandemic H1N1 strain and an influenza B strain. Mechanistic studies confirmed that compound 24 bound PA with a K d which equals to 1.88 μmol/L and disrupted the binding of PB1 to PA. The compound also decreased the lung viral titre in mice. In summary, we have identified a potent anti-influenza candidate with potency comparable to existing drugs and is effective against different viral strains. The therapeutic options for influenza infection have been limited by the occurrence of antiviral resistance, owing to the high mutation rate of viral proteins targeted by available drugs. To alleviate the public health burden of this issue, novel anti-influenza drugs are desired. In this study, we present our discovery of a novel class of indazole-containing compounds which exhibited favourable potency against both influenza A and B viruses. The EC50 of the most potent compounds were within low micromolar to nanomolar concentrations. Furthermore, we show that the mouse lung viral titre decreased due to treatment with compound 24. Thus our findings identify promising candidates for further development of anti-influenza drugs suitable for clinical use.
10.Sub-committee of Anesthesiology of Guangzhou Integrated Traditional Chinese and Western Medicine Society.
Yi LU ; Cunzhi LIU ; Wujun GENG ; Xiaozhen ZHENG ; Jingdun XIE ; Guangfang ZHANG ; Chao LIU ; Yun LI ; Yan QU ; Lei CHEN ; Xizhao HUANG ; Hang TIAN ; Yuhui LI ; Hongxin LI ; Heying ZHONG ; Ronggui TAO ; Jie ZHONG ; Yue ZHUANG ; Junyang MA ; Yan HU ; Jian FANG ; Gaofeng ZHAO ; Jianbin XIAO ; Weifeng TU ; Jiaze SUN ; Yuting DUAN ; Bao WANG
Journal of Southern Medical University 2025;45(8):1800-1808
OBJECTIVES:
To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and.
RESULTS:
Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications.
CONCLUSIONS
The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans
;
Medicine, Chinese Traditional
;
Cancer Pain/therapy*
;
Drugs, Chinese Herbal/therapeutic use*
;
Drug Delivery Systems
;
Pain Management/methods*
;
China


Result Analysis
Print
Save
E-mail