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.Meta-analysis of efficacy and safety of aspirin versus other anticoagulants in the prevention of thromboembolism after orthopedic surgery
Pei WANG ; Meng WEI ; Yingying TAO ; Yulei ZHAO ; Jing WANG ; Qiang ZHOU
China Pharmacy 2024;35(2):219-225
OBJECTIVE To evaluate the clinical efficacy and safety of aspirin versus other anticoagulants in the prevention of thromboembolism after orthopedic surgery. METHODS Retrieved from PubMed, Embase, the Cochrane Library, CNKI, Wanfang data and VIP, randomized controlled trials (RCTs) and cohort studies about aspirin (trial group) versus other anticoagulants (control group) were collected during the inception and June 1st, 2023. After literature screening, data extraction and quality evaluation, the meta-analysis was conducted by using RevMan 5.4 software. RESULTS A total of 22 studies were included, involving 9 RCTs and 13 cohort studies. RCT results showed that the incidences of deep vein thrombosis (DVT) [RR=1.81, 95%CI(1.36, 2.40), P<0.000 1] and postoperative pulmonary embolism (PE) [RR=1.55, 95%CI(1.01, 2.40), P=0.05] in trial group were significantly higher than control group. There was no statistically significant difference in the incidences of postoperative massive bleeding, postoperative surgical site infection, all-cause death, or any bleeding after surgery between 2 groups. In the cohort study, the incidence of any bleeding in trial group was significantly lower than control group [RR=0.71,95%CI (0.64, 0.79), P<0.000 1], while the differences in other indicators were not statistically significant (P>0.05). The results of subgroup analysis based on different anticoagulants showed that in RCT, the incidences of DVT and PE after surgery in patients using low-molecular-weight heparin (LMWH) were significantly lower than using aspirin (P<0.05); in the cohort study, the incidences of DVT and PE after surgery were significantly lower in patients using direct oral anticoagulants (DOAC) than using aspirin (P<0.05). There was no statistically significant difference in the incidence of major bleeding between patients using aspirin and using DOAC and LWMH (P>0.05) in both RCT and cohort study. CONCLUSIONS Aspirin is equally safe as other anticoagulants for the prevention of thromboembolism after orthopedic surgery, but its efficacy may not be as good as other anticoagulants. After orthopedic surgery, other anticoagulants should be preferred to prevent venous thromboembolism, and aspirin should be carefully considered.
7.Protective mechanism of rhubarb decoction against inflammatory damage of brain tissue in rats with mild hepatic encephalopathy: A study based on the PI3K/AKT/mTOR signaling pathway
Guangfa ZHANG ; Yingying CAI ; Long LIN ; Lei FU ; Fan YAO ; Meng WANG ; Rongzhen ZHANG ; Yueqiao CHEN ; Liangjiang HUANG ; Han WANG ; Yun SU ; Yanmei LAN ; Yingyu LE ; Dewen MAO ; Chun YAO
Journal of Clinical Hepatology 2024;40(2):312-318
ObjectiveTo investigate the role and possible mechanism of action of rhubarb decoction (RD) retention enema in improving inflammatory damage of brain tissue in a rat model of mild hepatic encephalopathy (MHE). MethodsA total of 60 male Sprague-Dawley rats were divided into blank group (CON group with 6 rats) and chronic liver cirrhosis modeling group with 54 rats using the complete randomization method. After 12 weeks, 40 rats with successful modeling which were confirmed to meet the requirements for MHE model by the Morris water maze test were randomly divided into model group (MOD group), lactulose group (LT group), low-dose RD group (RD1 group), middle-dose RD group (RD2 group), and high-dose RD group (RD3 group), with 8 rats in each group. The rats in the CON group and the MOD group were given retention enema with 2 mL of normal saline once a day; the rats in the LT group were given retention enema with 2 mL of lactulose at a dose of 22.5% once a day; the rats in the RD1, RD2, and RD3 groups were given retention enema with 2 mL RD at a dose of 2.5, 5.0, and 7.5 g/kg, respectively, once a day. After 10 days of treatment, the Morris water maze test was performed to analyze the spatial learning and memory abilities of rats. The rats were analyzed from the following aspects: behavioral status; the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) and the level of blood ammonia; pathological changes of liver tissue and brain tissue; the mRNA and protein expression levels of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) in brain tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the MOD group, the RD1, RD2, and RD3 groups had a significantly shorter escape latency (all P<0.01), significant reductions in the levels of ALT, AST, IL-1β, IL-6, TNF-α, and blood ammonia (all P<0.05), significant alleviation of the degeneration, necrosis, and inflammation of hepatocytes and brain cells, and significant reductions in the mRNA and protein expression levels of PI3K, AKT, and mTOR in brain tissue (all P<0.05), and the RD3 group had a better treatment outcome than the RD1 and RD2 groups. ConclusionRetention enema with RD can improve cognitive function and inflammatory damage of brain tissue in MHE rats, possibly by regulating the PI3K/AKT/mTOR signaling pathway.
8.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.
9.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.
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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