1.Effects of leonurine on myocardial injury in rats with coronary heart disease by regulating the GAS6/Axl signaling pathway
Wangtao MENG ; Dongling CUI ; Dongjing WU ; Chao CHEN ; Yingying ZHANG
China Pharmacy 2025;36(1):51-56
OBJECTIVE To explore the effects of leonurine on growth arrest-specific protein-6 (GAS6)/Axl signaling pathway, and clarify its mechanism of alleviating myocardial injury in rats with coronary heart disease. METHODS The rat model of coronary heart disease was constructed; successfully modeled rats were randomly separated into model group, leonurine low- dose and high-dose groups (intragastric administration of leonurine 25, 100 mg/kg+intraperitoneal injection of normal saline 75 mg/kg), and leonurine high-dose+GAS6/Axl signaling pathway inhibitor group (intragastric administration of leonurine 100 mg/kg+ intraperitoneal injection of R428 75 mg/kg), with 12 rats in each group. Additional 12 normal rats were selected as control group. Each administration group was given relevant medicine; control group and model group were given a constant volume of normal saline intragastrically and intraperitoneally, once a day, for 48 consecutive days. After administration, the heart function of rats, and serum levels of inflammatory factors and myocardial injury markers were detected; the pathological morphology of myocardial tissue was observed; the myocardial cell apoptosis rate, the expressions of apoptosis and GAS6/Axl signaling pathway-related proteins were determined. RESULTS Compared with control group, model group showed disorders in the arrangement of myocardial cells and myocardial fibers, hypertrophy of myocardial cells, and nuclear condensation; left ventricular ejection fraction, left ventricular fractional shortening, ratio of early-diastolic and late-diastolic motion velocity of the mitral ring, the protein expression of GAS6, B-cell lymphoma 2/B-cell lymphoma 2 associated X protein and phosphorylated Axl/Axl ratios were decreased significantly (P<0.05). The levels of tumor necrosis factor-α, interleukin-1β, interleukin-6, creatine kinase isoenzyme, troponin Ⅰ and myoglobin, the cell apoptosis rate, and cleaved caspase-3/caspase-3 ratio were increased significantly (P<0.05). Leonurine could obviously improve the above pathological conditions and detection indicators (P<0.05), and the effect of leonurine high-dose group was more significant than that of leonurine low-dose group (P<0.05); R428 treatment could reverse the ameliorating effect of high-dose of leonurine on myocardial injury in rats with coronary heart disease (P<0.05). CONCLUSIONS Leonurine can alleviate myocardial injury in rats with coronary heart disease, and its mechanism of action is related to the activation of the GAS6/Axl signaling pathway.
2.Exon Sequencing of HNF1β in Chinese Patients with Early-Onset Diabetes
Siqian GONG ; Hong LIAN ; Yating LI ; Xiaoling CAI ; Wei LIU ; Yingying LUO ; Meng LI ; Si-min ZHANG ; Rui ZHANG ; Lingli ZHOU ; Yu ZHU ; Qian REN ; Xiuying ZHANG ; Jing CHEN ; Jing WU ; Xianghai ZHOU ; Xirui WANG ; Xueyao HAN ; Linong JI
Diabetes & Metabolism Journal 2025;49(2):321-330
Background:
Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients.
Methods:
Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines.
Results:
Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher.
Conclusion
MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.
3.Exon Sequencing of HNF1β in Chinese Patients with Early-Onset Diabetes
Siqian GONG ; Hong LIAN ; Yating LI ; Xiaoling CAI ; Wei LIU ; Yingying LUO ; Meng LI ; Si-min ZHANG ; Rui ZHANG ; Lingli ZHOU ; Yu ZHU ; Qian REN ; Xiuying ZHANG ; Jing CHEN ; Jing WU ; Xianghai ZHOU ; Xirui WANG ; Xueyao HAN ; Linong JI
Diabetes & Metabolism Journal 2025;49(2):321-330
Background:
Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients.
Methods:
Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines.
Results:
Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher.
Conclusion
MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.
4.Exon Sequencing of HNF1β in Chinese Patients with Early-Onset Diabetes
Siqian GONG ; Hong LIAN ; Yating LI ; Xiaoling CAI ; Wei LIU ; Yingying LUO ; Meng LI ; Si-min ZHANG ; Rui ZHANG ; Lingli ZHOU ; Yu ZHU ; Qian REN ; Xiuying ZHANG ; Jing CHEN ; Jing WU ; Xianghai ZHOU ; Xirui WANG ; Xueyao HAN ; Linong JI
Diabetes & Metabolism Journal 2025;49(2):321-330
Background:
Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients.
Methods:
Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines.
Results:
Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher.
Conclusion
MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.
5.Exon Sequencing of HNF1β in Chinese Patients with Early-Onset Diabetes
Siqian GONG ; Hong LIAN ; Yating LI ; Xiaoling CAI ; Wei LIU ; Yingying LUO ; Meng LI ; Si-min ZHANG ; Rui ZHANG ; Lingli ZHOU ; Yu ZHU ; Qian REN ; Xiuying ZHANG ; Jing CHEN ; Jing WU ; Xianghai ZHOU ; Xirui WANG ; Xueyao HAN ; Linong JI
Diabetes & Metabolism Journal 2025;49(2):321-330
Background:
Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients.
Methods:
Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines.
Results:
Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher.
Conclusion
MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.
6.Characteristics of Oral Breath Odor Map of Chronic Atrophic Gastritis Patients with Dampness-Heat Syndrome: A Cross-Sectional Study
Xuejuan LIN ; Yanyu HUANG ; Long ZHU ; Donglin CAO ; Shanshan DING ; Xinghui LI ; Yingying HU ; Meng LAN ; Weirong HUANG
Journal of Traditional Chinese Medicine 2024;65(16):1687-1694
ObjectiveTo explore the recognition of oral breath odor map of chronic atrophic gastritis (CAG) patients with dampness-heat syndrome by electronic nose technique. MethodsPatients with chronic gastritis were recruited, including 60 cases in CAG group of dampness-heat syndrome, 50 cases in CAG group of non-dampness-heat syndrome, 60 cases in chronic non-atrophic gastritis (CNAG) group of dampness-heat syndrome, 50 cases in CNAG group of non-dampness-heat syndrome, and 30 cases of healthy volunteers were selected to set up the health control group. Ten cases in the CAG dampness-heat group and 50 cases in the CAG non-dampness-heat group were selected to form the CAG group, and 10 cases in CNAG dampness-heat group and 50 cases in CNAG non-dampness-heat group were selected to form the CNAG group. In addition to the health control group, the remaining patients were tested for Helicobacter pylori (Hp); the electronic nose (GISXM-MQWA01) was used to collect the oral breath odor of all the participants to draw the mapping, and amplitudes and slopes of each curve (including curves A, B, C, D, E, F, G, H, I, J) of the oral odor mapping of health control group, CAG group, CNAG group, CAG dampness-heat group, CAG non-dampness-heat group, and CNAG dampness-heat group was compared. The modified transformer model was used to classify the odor mapping characteristics, and the confusion matrix method was used to evaluate the classification model, with metrics including accuracy and area under ROC curve (AUC). ResultsThe Hp positivity rate in CAG dampness-heat group was 80.00% (48/60), CAG non-dampness-heat group was 62.00% (31/50), CNAG dampness-heat group was 46.67% (28/60), and CNAG non-dampness-heat group was 42.00% (21/50); the difference in Hp positivity rate between CAG dampness-heat group and CAG non-dampness-heat group was statistically significant (P<0.05). The amplitudes of response curves A, B, C, D, F, G, and I, and slopes of A and F in the odor mapping of the CAG group were lower than those in health control group, while the amplitude and slope of curve E were higher than those in the health control group and CNAG group (P<0.05 or P<0.01); The amplitude of the response curves A, B, C, D, F, G, and I, and slopes of A, D, and F in the CNAG group were lower than those in the health control group (P<0.05 or P<0.01). The amplitude of response curve D and slope of response curve J in the odor mapping of the CAG dampness-heat group were higher than those in CNAG dampness-heat group, the amplitude of curve F was lower than that in CAG non-dampness-heat group, and the amplitude of curve H and slopes of curve A, H, and J were higher than those in CAG non-dampness-heat group (P<0.05). The recognition accuracy of CAG group and health control group reached 77.78%, AUC = 0.88; the recognition accuracy of CAG group and CNAG group was 69.44%, AUC = 0.61; the recognition accuracy of CAG dampness-heat group and CAG non-dampness-heat group reached 75.8%, AUC=0.70. ConclusionElectronic nose technology can make a more accurate identification of the oral breath odor in CAG patients with dampness-heat syndrome, with a decrease in the amplitude of the curve F and an increase in the amplitude of the curve H and in the slopes of the curves A, H, and J may as the characteristics of their odor mapping.
7.Efficacy observation of cetrorelix combined with aspirin in preventing early-onset ovarian hyperstimulation syndrome
Yingying ZHANG ; Yile ZHANG ; Hao SHI ; Zhiqin BU ; Li YANG ; Yanlei MENG ; Yihong GUO
China Pharmacy 2024;35(16):2009-2012
OBJECTIVE To observe the efficacy of cetrorelix combined with aspirin in preventing early-onset ovarian hyperstimulation syndrome (OHSS). METHODS A retrospective analysis was conducted on clinical data from 38 early-onset OHSS patients, who received treatment in our hospital from January 1st to July 1st, 2022. These patients were divided into intervention group (19 cases) and control group (19 cases) according to the therapy regimen. On the first day after oocyte retrieval surgery, the control group was given aspirin enteric-coated tablets 100 mg orally until menstruation began. The intervention group was given cetrorelix for injection 0.25 mg subcutaneously, for consecutive 3 days+aspirin enteric-coated tablets (same usage and dosage as the control group). The first luteal phase, the degree of OHSS, and the ovarian volume, ascites volume, serum estradiol (E2), white blood cell count (WBC), hematocrit (HCT), neutrophil ratio (NEUT%), D-dimer (DD), prothrombin time (PT), fibrinogen (Fib) after oocyte retrieval surgery were observed and measured in 2 groups. RESULTS The first luteal phase was significantly shorter, and the proportions of median and severe OHSS cases were significantly lower in the intervention group compared to the control group (P<0.05 or P<0.01). After oocyte retrieval surgery, the intervention group showed significantly lower ovarian volume, ascites volume, serum E2, WBC, NEUT%, HCT, DD and Fib compared to the control group, but PT of intervention group was signiticantly higher than that of control group (P<0.05). CONCLUSIONS Cetrorelix combined with aspirin is more effective in preventing early-onset OHSS than aspirin alone.
8.Analysis of 25-hydroxyvitamin D levels and their influencing factors in mid-pregnancy women
Ying LI ; Yingying LI ; Ziwei LI ; Fanjing MENG
Shanghai Journal of Preventive Medicine 2024;36(8):779-782
ObjectiveTo investigate the levels of 25-hydroxyvitamin D [25 (OH) D] and its influencing factors in women during mid-pregnancy, and to provide an evidence for improving the vitamin D deficiency in pregnant women. MethodsA total of 220 pregnant women in the second trimester of pregnancy who underwent regular prenatal examinations at the Tianjin Binhai New Area Maternal and Child Health and Family Planning Service Center from February 2022 to February 2023 were selected as the research subjects. Basic clinical data of the pregnant women were collected. A 25 (OH) D level of ≥30 μg·L-1 was considered sufficient, while a level of <30 μg·L-1 was considered insufficient. Univariate analysis and multivariate logistic regression analysis were used to explore the factors influencing changes of 25 (OH) D levels in pregnant women. ResultsThe proportion of mid-pregnancy women with sufficient and insufficient 25 (OH) D levels were 15.9% (35/220) and 84.1% (185/220), respectively. Univariate analysis showed that 25 (OH) D level in mid-pregnancy women was associated with maternal age, season of blood collection, weekly duration of outdoor activities, dietary preferences, calcium supplementation, multivitamin supplementation, and passive or active smoking, and all the differences were statistically significant (all P<0.01). Multivariate logistic regression analysis revealed that women aged ≥35 years (OR=6.242, 95%CI: 2.501‒15.426, P<0.001), with dietary preferences (OR=1.091, 95%CI: 1.034‒1.150, P<0.001), and those who smoked or were exposed to passive smoking (OR=1.217, 95%CI: 1.084‒3.563, P<0.001), or during winter (OR=2.196, 95%CI: 1.593‒3.024, P<0.001) were more likely to have 25 (OH) D deficiency. Conversely, women engaged in ≥10 hours of outdoor activities per week (OR=3.406, 95%CI: 1.818‒5.386, P<0.001), supplemented with calcium (OR=1.811, 95%CI: 1.052‒3.116, P=0.032), and supplemented with multivitamins (OR=3.662, 95%CI: 1.864‒5.386, P<0.001) had a relatively lower risk of 25 (OH) D deficiency. The difference was statistically significant. ConclusionThe incidence of 25 (OH) D deficiency is high in mid-pregnancy women and is primarily associated with maternal age, season of blood collection, weekly duration of outdoor activities, dietary preferences, and supplementation of multivitamins. It is necessary to conduct 25 (OH) D level screening and provide necessary medical interventions and corresponding educational programs for pregnant women.
9.Effect of Gualou Xiebai Banxiatang on Myocardial Microangiogenesis and HIF-1α/VEGF-related Pathways in Myocardial Ischemia Model Rats
Wenhao CHEN ; Weishan MENG ; Hong LI ; Weiwei TIAN ; Qi ZHANG ; Yingying TAN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(17):1-9
ObjectiveTo investigate the effect of Gualou Xiebai Banxiatang on cardiac function and myocardial histopathological changes in rats with ischemic myocardial injury, and to observe the effect of myocardial microvascular density (MVD), phosphatidylinositol 3-kinase (PI3K), mammalian target of rapamycin (mTOR), hypoxia-inducible factor-1 alpha (HIF-1α), and vascular endothelial growth factor (VEGF) signaling pathways on myocardial microangiogenesis. MethodSeventy male SD rats were randomly selected, with six rats in the normal group. The remaining rats were fed a high-fat diet and injected with isoproterenol hydrochloride (ISO,80 mg·kg-1·d-1, 2 d) to induce a hyperlipidemia-based ischemic heart disease model. After successful modeling, the rats were randomly divided into the model group, high, medium, and low dose groups of Gualou Xiebai Banxiatang, and the metoprolol group. The high, medium, and low dose groups of Gualou Xiebai Banxiatang were given Gualou Xiebai Banxiatang at 10.42, 5.21, 2.61 g·kg-1·d-1, respectively, while the metoprolol group was given metoprolol at 2.6 mg·kg-1·d-1. Both the normal and model groups were given an equivalent volume of physiological saline for 28 days. After the intervention, relevant tests were conducted, and serum was collected to measure heart function-related indicators. Hematoxylin-eosin (HE) and Masson staining were performed on ventricular tissue to observe pathological changes under a light microscope. Immunohistochemistry (IHC) was used to detect the positive expression of platelet endothelial cell adhesion molecule (CD31). Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression of N-terminal pro-brain natriuretic peptide (NT-proBNP) and VEGF. Western blot was used to detect the protein expression levels of PI3K/mTOR/HIF-1α/VEGF. ResultCompared with the normal group, the model group showed significantly increased serum levels of LDH, CK, CK-MB, NT-proBNP, and VEGF (P<0.01), significantly increased collagen volume fraction (CVF) (P<0.01), significantly decreased MVD (P<0.01), and elevated protein expression levels of PI3K, mTOR, HIF-1α, and VEGF (P<0.05, P<0.01). Compared with the model group, the metoprolol group had significantly lower serum levels of LDH, CK, CK-MB, and NT-proBNP (P<0.01), significantly higher VEGF levels (P<0.01), significantly decreased CVF (P<0.01), significantly increased MVD (P<0.01), and significantly increased protein expression levels of PI3K, mTOR, and VEGF (P<0.01), with no statistically significant change in HIF-1α protein expression. Compared with the model group, the high and medium dose groups of Gualou Xiebai Banxiatang had decreased serum levels of LDH, CK, CK-MB, and NT-proBNP (P<0.05, P<0.01), increased VEGF levels (P<0.05, P<0.01), significantly reduced CVF (P<0.01), increased MVD (P<0.05, P<0.01), and significantly increased protein levels of PI3K, mTOR, HIF-1α, and VEGF (P<0.01). In the low dose group of Gualou Xiebai Banxiatang, compared with the model group, serum levels of LDH and NT-proBNP were decreased (P<0.05), VEGF was increased (P<0.05). Moreover, CVF was decreased (P<0.05), and the protein expression levels of PI3K, mTOR, HIF-1α, and VEGF were significantly increased (P<0.01). ConclusionGualou Xiebai Banxiatang can improve cardiac function, reduce myocardial pathological damage, enhance endothelial cell function, promote myocardial microvascular formation, and upregulate the expression of PI3K, mTOR, HIF-1α, and VEGF proteins in myocardial tissue in rats with ischemic myocardial injury.
10.Research Progress on Traditional Chinese Medicine in Treating Viral Hepatitis: A Review
Xiaojie FENG ; Junjie YU ; Yingying SUI ; Lina WANG ; Fangang MENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(13):289-298
Viral hepatitis is an important cause of liver cirrhosis and liver cancer, which has become a major public health problem in the world. Traditional Chinese medicine has unique advantages in treating viral hepatitis, which can inhibit virus replication and enhance immunity. It can effectively prevent liver fibrosis and canceration, improving liver function and symptoms significantly with definite clinical curative effects, a high level of safety, and seldom drug resistance. In addition, it reduces the side effects of western medicine, achieving the effect of synergy and attenuation while reducing the recurrence rate of patients after drug withdrawal. Attention has been paid to the research on the treatment of viral hepatitis with traditional Chinese medicine, and great progress has been made in experimental research and clinical practice. In this paper, the research progress of traditional Chinese medicine in the treatment of viral hepatitis at home and abroad in recent five years was systematically reviewed. Modern research has confirmed that traditional Chinese medicine can play a role in the treatment of viral hepatitis by directly or indirectly inhibiting the virus, anti-inflammatory, anti-fibrosis, anti-oxidation, regulating immunity, regulating autophagy, and other signal pathways. In clinics, traditional Chinese medicine compound or combined with western medicine is often adopted to ameliorate the clinical symptoms of patients such as fatigue and loss of appetite, improve the immune mechanism of the body, enhance the antiviral ability, shorten the treatment course of patients and improve their quality of life. The research provides a reference for pharmacological research, clinical research, and new drug development for viral hepatitis.

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