1.Effect of Modified Chaihu Shugansan on CaMKⅡ/CREB Signaling Pathway in Rats with Myocardial Ischemia and Depression
Fen WAN ; Xiaohong LI ; Ying CHEN ; Yangyu PAN ; Yanna LUO ; Fangge LU ; Chuncheng ZHENG ; Pengyun KONG ; Chengxiang WANG ; Liqiang YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):1-11
ObjectiveTo observe the effects of modified Chaihu Shugansan on the calmodulin-dependent protein kinase Ⅱ(CaMKⅡ)/cAMP-response element binding protein (CREB) signaling pathway in the hippocampus and heart tissue of a rat model with myocardial ischemia and depression and explore the mechanism by which this formula prevents and treats coronary heart disease combined with depression. MethodsThe model of myocardial ischemia combined with depression was established by high-fat diet, intraperitoneal injection of isoproterenol (ISO), and chronic unpredictable mild stress (CUMS). A total of 108 SD male rats were randomly divided into normal group, model group, high (23.4 g·kg-1), medium (11.7 g·kg-1), and low (5.85 g·kg-1) dose groups of modified Chaihu Shugansan, CaMKⅡ inhibitor (KN93) group, and KN93 + high, medium, and low dose groups of modified Chaihu Shugansan, with 12 rats in each group. From the first day of modeling to the end of modeling, drugs were administered once a day. In the seventh and eighth weeks, the KN93 group and the KN93 + high, medium, and low dose groups of modified Chaihu Shugansan were intraperitoneally injected with KN93 three times weekly. At the end of the eighth week, behavioral tests including sucrose preference, open field, and elevated plus maze were conducted. Electrocardiogram (ECG) lead Ⅱ changes were observed in each group of rats, and hematoxylin-eosin (HE) staining was performed to observe changes in heart tissue. Serum levels of triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and lactate dehydrogenase (LDH) were measured by using an enzyme-labeled instrument. Creatine kinase (CK) and creatine kinase-MB (CK-MB) were detected by ultraviolet spectrophotometry, while serum monocyte chemoattractant protein-1 (MCP-1) was measured by enzyme-linked immunosorbent assay (ELISA). Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect mRNA expression of CaMKⅡ and CREB in hippocampal and heart tissue, and Western blot was performed to assess protein expression of CaMKⅡ, phosphorylated (p)-CaMKⅡ, CREB, and p-CREB. ResultsCompared to the normal group, the model group showed significant reductions in sucrose preference rate, total activity distance in the open field, number of entries into the center area of the open field, and percentage of entries into the open arms of the elevated plus maze (P<0.01). The ECG showed ST-segment elevation, and HE staining showed serious degeneration of myocardial fibers, disordered arrangement, and infiltration of a large number of inflammatory cells. In addition, serum TC and LDL levels increased (P<0.01), and HDL level decreased (P<0.01). CK, CK-MB, LDH, and MCP-1 levels significantly increased (P<0.05, P<0.01). The mRNA expression of CaMKⅡ and CREB and the protein expression of p-CaMKⅡ and p-CREB decreased in the hippocampal tissue (P<0.05, P<0.01), but those increased in the heart tissue (P<0.01). Compared to the model group, the high, medium, and low dose groups of modified Chaihu Shugansan showed improvements in these abnormalities. The KN93 group had reduced sucrose preference, total activity distance in the open field, number of entries into the center area of the open field, and percentage of entries into the open arms of the elevated plus maze (P<0.01), as well as decreased serum CK, CK-MB, LDH, and MCP-1 levels (P<0.05, P<0.01). KN93 also reduced ST-segment elevation, alleviated the degeneration degree of myocardial fibrosis, and lowered inflammatory cell infiltration. The mRNA expression of CaMKⅡ and CREB and the protein expression of p-CaMKⅡ and p-CREB in both the hippocampal and heart tissue were reduced (P<0.05, P<0.01). The KN93 + high, medium, and low dose groups of modified Chaihu Shugansan showed further improvements in these abnormalities compared to the KN93 group. ConclusionThe modified Chaihu Shugansan exerts antidepressant and myocardial protective effects in rats with myocardial ischemia and depression, possibly related to bidirectional regulation of the CaMKⅡ/CREB signaling pathway, with the high-dose modified Chaihu Shugansan showing the best effects.
2.Survey on Regional Hierarchical and Transferal Management of Severe Post-partum Hemorrhage in Beijing
Yike YANG ; Huan CHEN ; Yangyu ZHAO
Journal of Practical Obstetrics and Gynecology 2024;40(3):186-191
Objective:To assess the current state of care for Severe Postpartum Hemorrhage(SPPH)in refer-ral centers and non-referral centers,and to propose enhanced strategies for the regional prevention and manage-ment of SPPH.Methods:The clinical data of patients with SPPH,defined as postpartum blood loss≥1500 ml or transfusion of blood products≥1000 ml,in two districts of Beijing from January 2021 to June 2023 were retrospec-tively analyzed.A total of 201 cases of SPPH were included and they were divided into 125 cases in the referral center group and 76 cases in the non-referral center group based on whether they were city level referral centers.The clinical characteristics between these two groups were compared.Furthermore,a stratified analysis was con-ducted using a Logistic regression model to identify the risk factors associated with massive postpartum hemor-rhage,defined as postpartum hemorrhage≥4000 ml,transfusion requirements exceeding suspended red blood cells(RBC)>10 U and(or)plasma>1000 ml.Results:Analysis of cases presenting with SPPH between the two study groups showed that patients in the referral center group exhibited advanced maternal age,smaller gestation-al weeks at delivery and a higher proportion of high-risk factors compared to those in the non-referral center group,and the difference was statistically significant(P<0.05).The primary cause of SPPH in the referral center group was placental factors,while uterine atony was identified as the main factor in the non-referral center group,and this difference was statistically significant(P<0.05).Additionally,within the non-referral center group,there was a higher amount of blood loss during cesarean section,lower proportion of B-Lynch suture/vascular suture ligation,and higher proportion of uterine packing(P<0.05).Furthermore,compared to the referral center group,there were significantly higher incidences of plasma transfution volume,return to operating room for further inter-vention or exploratory laparotomy procedures after initial delivery and complications related to postpartum hemor-rhage observed in the non-referral center group(P<0.05).Moreover,it was noted that there were more cases of massive postpartum hemorrhagic disease reported in the non-referral center group than in the referral center group(P<0.05).In massive postpartum hemorrhage cases analyzed,referring centers had a higher percentage of patients presenting with multiple high-risk factors for postpartum hemorrhage during pregnancy when compared to non-referring centers(71.4%vs.33.3%,P<0.05).Placental factors accounted for majority causes leading to hemorrhage within referring centers(57.1%),whereas both uterine atony and placental factors played major roles within non-referring centers′cases(42.9%,28.6%).The multivariate Logistic regression analysis revealed that non-referral center delivery(aOR 3.47,95%CI 1.40-9.18)and a history of multiple intrauterine operations(aOR 12.63,95%CI 1.24-131.30)were identified as significant risk factors for massive postpartum hemor-rhage.Conclusions:The outcomes of high-risk pregnant women referral management in the region exhibit an im-provement,necessitating the reinforcement of training in non-referral midwifery institutions regarding identification of high-risk factors,surgical suture techniques,and comprehensive SPPH management to avert excessive bleed-ing and blood transfusion.
3.Analysis of Animal Models of Post-infectious Irritable Bowel Syndrome Based on Characteristics of Clinical Symptoms of Traditional Chinese and Western Medicine
Lu'an XIE ; Yangyu ZHANG ; Xiaoxia CHEN ; Zhendong PAN ; Yiling YANG ; Shi HUANG
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(1):92-102
Objective This paper summarizes and evaluates the existing animal models of Post-infectious irritable bowel syndrome(PI-IBS)based on the clinical diagnostic criteria and symptom characteristics of PI-IBS in Chinese and western medicine.The goal of this study is to seek out animal models with a high degree of clinical agreement between Chinese and western medicine,and to provide an accurate animal model for the prevention and treatment of PI-IBS in traditional Chinese medicine.Methods The animal strains,modelling methods,and mechanisms of the existing PI-IBS animal models were summarized based on the clinical diagnostic features and symptomatology of PI-IBS,as well as the degree of match was evaluated and the strengths and weaknesses of the preparation of animal models were analyzed,by reviewing the articles related to PI-IBS animal experiments and the preparation of animal models.Results A thorough analysis discovered that Campylobacter jejuni infection model,Trichinella infection model,and liver depression and spleen deficiency syndrome in models of disease and symptom combination showed a comparatively high level of clinical agreement between Chinese and western medicine.Conclusion The existing PI-IBS models had the high degree of coincidence with western medicine,Chinese medicine four diagnoses and syndrome are generally less embodied and collected in the modeling process.The primary symptoms in Chinese medicine diagnosis are primarily based on the observation of animal apparent behaviors,while the observation of the sub-syndrome manifestations is relatively less,which results in failure of judgment of TCM syndrome types.Therefore,it is still necessary to further standardize the criteria for evaluating symptoms and the techniques for identifying disease-syndrome combination animal models.PI-IBS model with the syndrome-clinical characteristics in Chinese and western medicine has significant application value and prospects in the future.The multifactorial composite method of western medicine pathological injury+Chinese medicine etiological stimulation can establish a PI-IBS model with a higher degree of coincidence,which can provide theoretical support for the study of the pathogenesis of PI-IBS,the difference of syndrome,and the prevention and treatment with integrative Chinese and western medicine.It is crucial to guide the clinical diagnosis and treatment of PI-IBS.
4.FBXW7 promotes ferroptosis in head and neck squamous cell carcinoma cells through inhibiting c-Myc/SOX2/SLC7A11
Yiren CHEN ; Zhenyuan ZHAO ; Yangyu ZHENG ; Wei ZHANG ; Xiaomeng SONG
STOMATOLOGY 2024;44(6):426-432
Objective To explore the effect of FBXW7 on ferroptosis in head and neck squamous cell carcinoma.Methods Head and neck squamous cell lines HN4 and HN6 were cultured in vitro.FBXW7 and SOX2 overexpression plasmids were constructed,and the plasmids were stably transfected into cell lines.The overexpression transfection efficiency was verified at the transcription level and protein level by qRT-PCR and Western blot experiments,respectively.The lipid peroxidation levels of head and neck squamous cell carcinoma cells with overexpressing FBXW7 were verified by measuring malondialdehyde(MDA),glutathione(GSH),and reactive ox-ygen species(ROS)levels.After treating cells with ferroptosis inhibitor Fer-1,the changes in cell viability were further detected to ver-ify the effect of FBXW7 on ferroptosis.The effect of transfection of the overexpressed plasmid on cellular pathways was detected by Western blot.Results HN4 and HN6 cell lines showed increased levels of lipid peroxidation after overexpression of FBXW7,and the ferroptosis inhibitor Fer-1 was able to effectively reverse the ferroptosis induced by overexpression of FBXW7.Western blot assay results showed that overexpression of FBXW7 reduced the expression of c-Myc,SOX2 and SLC7A11.Conclusion FBXW7 regulates the ex-pression of SOX2-SLC7A11 by degrading c-Myc,thereby effectively regulating ferroptosis in HNSCC.
5.Recommendations for the diagnosis and treatment of maternal SARS-CoV-2 infection
Dunjin CHEN ; Yue DAI ; Xinghui LIU ; Hongbo QI ; Chen WANG ; Lan WANG ; Yuan WEI ; Xiaochao XU ; Chuan ZHANG ; Lingli ZHANG ; Yuquan ZHANG ; Ruihua ZHAO ; Yangyu ZHAO ; Borong ZHOU ; Ailing WANG ; Huixia YANG ; Li SONG
Chinese Journal of Perinatal Medicine 2023;26(6):441-447
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread worldwide and threatened human's health. With the passing of time, the epidemiology of coronavirus disease 2019 evolves and the knowledge of SARS-CoV-2 infection accumu-lates. To further improve the scientific and standardized diagnosis and treatment of maternal SARS-CoV-2 infection in China, the Chinese Society of Perinatal Medicine of Chinese Medical Association commissioned leading experts to develop the Recommendations for the Diagnosis and Treatment of Maternal SARS-CoV-2 Infection under the guidance of the Maternal and Child Health Department of the National Health Commission. This recommendations includes the epidemiology, diagnosis, management, maternal care, medication treatment, care of birth and newborns, and psychological support associated with maternal SARS-CoV-2 infection. It is hoped that the recommendations will effectively help the clinical management of maternal SARS-CoV-2 infection.
6.The progress of MRI in the diagnosis and prediction of placental implantation diseases
Journal of Chinese Physician 2023;25(9):1306-1308,1312
Magnetic resonance imaging (MRI) is a commonly used method for preoperative diagnosis and prediction of placental implantation disease (PAS), and various MRI features can be used for predicting PAS. In recent years, research has mainly focused on the predictive efficacy of MRI implantation signs. With the development of technology, functional MRI has also begun to be applied in the diagnosis of PAS. The imaging omics analysis based on MRI images, deep learning assisted by artificial intelligence, and three-dimensional image reconstruction have all proposed new application ideas for MRI in the diagnosis, prediction, and surgical planning of PAS from a new perspective. This article elaborates on the progress and clinical auxiliary effects of MRI in the diagnosis and prediction of PAS.
7.Factors influencing pH value of umbilical arterial blood gas analysis in preterm infants
Qingqing WANG ; Meihua PIAO ; Lian CHEN ; Yangyu ZHAO ; Tongyan HAN
Chinese Journal of Perinatal Medicine 2022;25(6):439-442
Objective:To analyze the factors influencing pH value in umbilical arterial blood gas (UABG) analysis in preterm infants.Methods:A retrospective study was conducted on live singleton preterm infants ( n=573) who received UABG analysis in Peking University Third Hospital from January 2017 to February 2019. Analysis of variance, independent sample t-test, Spearman's or Pearson's correlation analysis, or linear regression analysis was used to analyze the influencing factors. Results:There was no significant difference in UABG pH value between preterm infants of different gestational ages (F=1.74, P=0.077). Spearman's correlation analysis found no correlation between gestational age and UABG pH value in premature infants ( r=0.003, P=0.940), and neither did Pearson's correlation between birth weight and pH value ( r=0.025, P=0.548). UABG pH value in preterm infants was linearly correlated with vaginal delivery ( t=-5.72, P<0.001), gestational hypertension ( t=-3.99, P<0.001) and placental abruption ( t=-4.52, P<0.001). Conclusions:Preterm infants at different gestational ages show a similar pH value in UABG. For those born to mothers with gestational hypertension or placental abruption, when vaginal delivery is pending, close monitoring and full preparation for resuscitation are necessary.
8.Complement Inhibitors in Rare Diseases
Cai YUE ; Yali DU ; Yangyu HUANG ; Limeng CHEN ; Yuzhou GUAN ; Bing HAN
JOURNAL OF RARE DISEASES 2022;1(4):391-399
The complement system is a self-protection mechanism of the human body. The abnormal activation of the complement system is involved in the occurrence and development of various diseases. The application of complement inhibitors in many rare diseases was a milestone in leading to the progress of such disease as paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), and others. Recently, the application of complement inhibitors has gradually expanded to other complement-related diseases. This review summarizes the literature on the current application of complement inhibitors in rare diseases and looks into the prospects of the application in the rare diseases.
9.Predictive value of MRI image-based scoring model for diagnosis and adverse clinical outcomes of invasive placenta accrete
Lian CHEN ; Ming CHEN ; Xinlong PEI ; Huifeng SHI ; Xiaoming SHI ; Yuanyuan WANG ; Yangyu ZHAO
Chinese Journal of Perinatal Medicine 2021;24(1):32-39
Objective:To explore the predictive value of a scoring model based on MRI images for diagnosing invasive placenta accreta and associated adverse clinical outcomes.Methods:This retrospective cohort study involved 260 patients delivered at Peking University Third Hospital from January 2015 to December 2018, who were suspected to be placenta accreta with two or more ultrasound image findings and underwent MRI examination. Placenta accreta was finally diagnosed and classified based on the intraoperative clinical findings or pathological examination. Adverse clinical outcomes were defined as intraoperative bleeding ≥1 500 ml and/or having hysterectomy. Quantitative and qualitative interpretation of five MRI signs were performed, including intraplacental low-intensity band on T2 weighted imaging, abnormal intraplacental vascularization, vascularization of uterovesical interface, uterine bulging and cervical involvement. Chi-square and t test were used for univariate analysis of the five MRI signs and the receiver operating characteristics (ROC) curve of each MRI sign for predicting invasive placenta accreta and adverse clinical outcomes were drawn. The predictive value was assigned as 1 when ≥ the cutoffs that matched to the maximum Yoden index values, and was assigned as 0 when below the cutoffs. A scoring model based on the five MRI signs was established, ROC curves of the model for predicting invasive placenta accreta and adverse clinical outcomes were drawn and the area under the curve (AUC), sensitivity, specificity and Youden index were calculated. Results:(1) Univariate analysis showed that all five MRI signs were significantly associated with invasive placenta accreta and adverse clinical outcomes. Except for cervical involvement, the other four signs had an AUC value of greater than 0.5 in predicting invasive placenta accreta and adverse clinical outcomes. (2) The predictive cut-off values of abnormal intraplacental vascularization image and intraplacental dark band area on T2 weighted imaging were 2.0 cm 2 and 0.6 cm 2, respectively, and were all 1.0 for the other three signs. The AUC value of MRI signs-based scoring model for predicting invasive placenta accreta was 0.863. When the score was ≥ 2 points, the diagnostic sensitivity was 0.836 and the specificity was 0.726. The scoring model predicted adverse clinical outcomes with an AUC of 0.841. When the score was ≥3 points, the predictive sensitivity was 0.707 and the specificity was 0.818. Conclusions:The scoring model based on MRI signs is of good value for the diagnosis of invasive placenta accreta and the prediction of adverse clinical outcomes.
10.The vicK gene of Streptococcus mutans mediates its cariogenicity via exopolysaccharides metabolism.
Yalan DENG ; Yingming YANG ; Bin ZHANG ; Hong CHEN ; Yangyu LU ; Shirui REN ; Lei LEI ; Tao HU
International Journal of Oral Science 2021;13(1):45-45
Streptococcus mutans (S. mutans) is generally regarded as a major contributor to dental caries because of its ability to synthesize extracellular polysaccharides (EPS) that aid in the formation of plaque biofilm. The VicRKX system of S. mutans plays an important role in biofilm formation. The aim of this study was to investigate the effects of vicK gene on specific characteristics of EPS in S. mutans biofilm. We constructed single-species biofilms formed by different mutants of vicK gene. Production and distribution of EPS were detected through atomic force microscopy, scanning electron microscopy and confocal laser scanning microscopy. Microcosmic structures of EPS were analyzed by gel permeation chromatography and gas chromatography-mass spectrometry. Cariogenicity of the vicK mutant was assessed in a specific pathogen-free rat model. Transcriptional levels of cariogenicity-associated genes were confirmed by quantitative real-time polymerase chain reaction. The results showed that deletion of vicK gene suppressed biofilm formation as well as EPS production, and EPS were synthesized mostly around the cells. Molecular weight and monosaccharide components underwent evident alterations. Biofilms formed in vivo were sparse and contributed a decreased degree of caries. Moreover, expressional levels of genes related to EPS synthesis were down-regulated, except for gtfB. Our report demonstrates that vicK gene enhances biofilm formation and subsequent caries development. And this may due to its regulations on EPS metabolism, like synthesis or microcosmic features of EPS. This study suggests that vicK gene and EPS can be considered as promising targets to modulate dental caries.
Animals
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Biofilms
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Dental Caries
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Dental Plaque
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Rats
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Streptococcus mutans/genetics*

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