1.Effects of Zuogui Jiangtang Qingzhi Formula on the cGAS/STING/TBK1 signaling pathway in mice with type 2 diabetes mellitus combined with non-alcoholic fatty liver disease
Yangyang GOU ; Jiahui MA ; Cong CHEN
Journal of Beijing University of Traditional Chinese Medicine 2025;48(3):370-378
Objective:
To investigate how Zuogui Jiangtang Qingzhi Formula (ZGJTQZF), a traditional Chinese medicine compound for lowering blood glucose levels and clearing lipids based on Zuogui Pill, regulates the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING)/TANK-binding kinase 1 (TBK1) signaling pathway to improve type 2 diabetes mellitus combined with non-alcoholic fatty liver disease.
Methods:
According to fasting blood glucose (FBG) levels, body weight, and sex, 40 MKR mice, with half being male and the other half female, were randomly divided into four groups: blank, model, ZGJTQZF (29.6 g/kg), metformin + simvastatin ([65.0+ 2.6] mg/kg), 10 mice per group, and a normal group consisting of 10 age-matched FVB mice. Mice in all groups, except in the normal and blank groups, were fed a high-fat diet for 8 weeks to induce the disease model. Each group received daily gavage of the respective treatments for 8 weeks after successful modeling. Various parameters were measured, including FBG, liver function (alanine aminotransferase [ALT] and aspartate transaminase [AST]), and blood lipids (triglyceride [TG] and total cholesterol [TC]). Serum levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were determined using enzyme-linked immunosorbent assays. Histological liver changes were examined using transmission electron and optical microscope. cGAS, STING, and TBK1 protein and mRNA expression levels in liver tissues were detected using Western blotting and real-time PCR, respectively.
Results:
Compared with the normal group, the model group exhibited significant fat accumulation in hepatocytes and liver damage. Additionally, FBG, ALT, AST, serum TNF-α, IL-6, cGAS, STING and TBK1 expression levels in liver tissues were significantly elevated (P<0.05). Treatment with ZGJTQZF and metformin + simvastatin significantly improved FBG, ALT, AST, TG, TC, TNF-α, and IL-6 (P<0.01). Histologically, hepatic steatosis was notably alleviated. Expression of protein and mRNA of cGAS, STING, and TBK1 in liver tissues was significantly reduced (P<0.05).
Conclusion
ZGJTQZF improves lipid and glucose metabolism, mitigates liver injury, and reduces inflammatory markers in MKR mice. These effects may be mediated through the regulation of the cGAS/STING/TBK1 signaling pathway.
2.Automatic acquisition and analytic procedure of acupuncture manipulation based on optical navigation.
Changshuai ZHANG ; Zihao FENG ; Weichao CHANG ; Weigang MA ; Yongjian WU ; Haiming LI ; Xingfang PAN ; Haiyan REN ; Yangyang LIU ; Zhaoshui HE ; Wenjun TAN
Chinese Acupuncture & Moxibustion 2025;45(10):1383-1390
This paper presents an automatic acquisition and analytic procedure of acupuncture manipulation based on optical navigation, aiming at solving the shortcomings of existing acquisition methods of acupuncture manipulation. An acquisition holder installed at the handle tail of filiform needle was designed to display the movement trajectory of the needle during acupuncture delivery by collecting the movement trajectory of holder. The 3-month old male Bama miniature pig was selected as the experimental subject, and 6 points, "Bojian" "Qiangfeng" "Housanli" "Xiaokua" "Huiyang" (BL35) and "Baihui" (GV20), were selected during acupuncture manipulation. The optical navigation system was used to collect the real-time data, and these data were per-processed and analyzed using mean filtering and Fourier transform. The acupuncture procedure was divided into 3 stages, inserting, lifting-thrusting, and twisting. The results showed that the accuracy was 96.3% at lifting-thrusting stage, and that was 100.0% at twisting stage. The decomposition effect of the entire procedure was satisfactory. This study provides a new approach to the quantitative analysis of acupuncture manipulation. In the future, it needs to further optimize the algorithm and expand the sample size so as to improve the accuracy of this analytic technique.
Acupuncture Therapy/methods*
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Male
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Animals
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Swine
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Acupuncture Points
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Humans
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Swine, Miniature
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Needles
3.Association of pregnancy factors with cow's milk protein allergy in infants
Yangyang LI ; Lin HOU ; Zijun MA ; Shanyamei HUANG ; Jie LIU ; Chaomei ZENG ; Jiong QIN
Journal of Peking University(Health Sciences) 2024;56(1):144-149
Objective:To preliminarily explore the association of pregnancy factors with cow's milk protein allergy in infants.Methods:This study was based on data from a subcohort of a study called ge-netic susceptibility to cow's milk allergy in Chinese children,including infants born in Peking University People's Hospital between March 1,2020,and December 31,2020.The infants were divided into a cow's milk protein allergy(CMPA)group and a control group according to whether they had developed cow's milk protein allergy at the age of 1 year.We retrospectively collected the clinical data of infants and their mothers before and during pregnancy,and analyzed the association of multiple factors during pregnancy with cow's milk protein allergy in infants.Results:A total of 278 infants were enrolled in this study,including 52 infants with CMPA and 226 infants without CMPA.Among them,there were 143 boys and 135 girls.The proportion of male infants in the CMPA group(69.2%)was higher than that in the control group(47.3%),and the difference was statistically significant(P=0.004).There were no significant differences in the distribution of birth weight,gestational age at birth,low-birth-weight in-fants,premature,umbilical cord entangle neck,and neonatal asphyxia between the CMPA group and the control group(P>0.05).The proportion of mothers complicated with autoimmune diseases,anemia or antibiotics exposure during pregnancy in the CMPA group was higher than that in the control group,and there were statistical differences between the two groups(P<0.05).There was no significant difference in the distribution of other pregnancy complications between the two groups(P>0.05),such as eclamp-sia/preeclampsia,chronic hypertension/gestational hypertension,diabetes/gestational diabetes,thyroid diseases,and so on.There was no significant difference in the overall distribution of some blood routine indexes during pregnancy between the CMPA group and the control group(P>0.05).Multivariate Lo-gistic regression analysis showed that male infant,mothers complicated with autoimmune diseases or ane-mia,antibiotic exposure during pregnancy were independent risk factors for cow's milk protein allergy.Conclusion:Male infant,mothers complicated with autoimmune diseases or anemia,antibiotic exposure during pregnancy were independent risk factors for cow's milk protein allergy.
4.Relationship between serum miR-21 and miR-27b levels and prognosis of patients with renal clear cell carcinoma
Shuang CHEN ; Na YANG ; Yudong HUANG ; Xiangfeng KONG ; Jintao LI ; Yizhong TANG ; Kex-Iong MA ; Yangyang ZHANG ; Yuandong ZHANG ; Chengde REN
The Journal of Practical Medicine 2024;40(3):343-347
Objective To explore the relationship between serum miRNA-21 and miR-27b levels and prognosis of patients with renal clear cell carcinoma.Methods A total of 118 patients with renal clear cell carcinoma admitted to the Qinghai University Hospital from February 2019 to April 2021 were selected as the study subjects,and another 118 healthy patients in the same period as the control group.Real time fluorescence quantitative polymerase chain reaction(PCR)was used to detect the expression of miR-21 and miR-27b in the serum of all subjects.The relative expression levels of serum miR-21 and miR-27b between the patients with renal clear cell carcinoma and healthy control patients were compared.The expression and correlation of serum miR-21 and miR-27b in the patients with renal clear cell carcinoma of different pathological stages and Fuhrman grading were analyzed.The relationship between the expression of serum miR-21 and miR-27b and the survival and prognosis of the patients was explored as well.Results The expression levels of serum miR-21 and miR-27b in the patients with renal clear cell carcinoma were higher than those in the healthy control group(P<0.05).The serum miR-21 expression level in stage Ⅲ patients was higher than in stageⅠ(P<0.05),while the serum miR-21 expression level in the stage Ⅳ patients was higher than that in stagesⅠ,Ⅱ,and Ⅲ(P<0.05).The expression level of miR-27b in the serum of patients gradually increased across the four stages,with a significant difference(P<0.05).The pathological staging was positively correlated with the expression of miR-21 and miR-27b(P<0.001).The expression levels of miR-21 and miR-27b in serum of patients gradually increased across grades Ⅰ,Ⅱ and Ⅲ by Fuhrman grading,with significant difference(P<0.05).Fuhrman grading was positively correlated with the serum miR-21 and miR-27b expression(P<0.001).There was a statistically significant difference in the survival curve between the miR-21 high expression group and the low expression group(P<0.05).There was a statistically significant difference in the survival curve between the high expression group and the low expression group of miR-27b(P<0.05).Conclusion The expression levels of serum miR-21 and miR-27b in patients with renal clear cell carcinoma is indicative of the progression and prognosis of the patient's condition.
5.Rho kinase inhibitor Y27632 promotes survival of human induced pluripotent stem cells during differentiation into functional midbrain dopaminergic progenitor cells in vitro
Yangyang LI ; Jiajia XU ; Chengcheng JIANG ; Zilong CHEN ; Ying CHEN ; Mengjiao YING ; Ao WANG ; Caiyun MA ; Chunjing WANG ; Yu GUO ; Changqing LIU
Journal of Southern Medical University 2024;44(2):236-243
Objective To improve the efficiency of induced differentiation of primitive neural epithelial cells derived from human induced pluripotent stem cells(hiPSCs-NECs)into functional midbrain dopaminergic progenitor cells(DAPs).Methods HiPSCs were cultured in mTeSRTM medium containing DMH1(10 μmol/L),SB431542(10 μmol/L),SHH(200 ng/mL),FGF8(100 ng/mL),purmorphamine(2 μmol/L),CHIR99021(3 μmol/L),and N2(1%)for 12 days to induce their differentiation into primitive neuroepithelial cells(NECs).The hiPSCs-NECs were digested with collagenase IV and then cultured in neurobasal medium supplemented with 1%N2,2%B27-A,BDNF(10 ng/mL),GDNF(10 ng/mL),AA,TGF-β,cAMP,and 1%GlutaMax in the presence of different concentrations of Rho kinase inhibitor Y27632,and the culture medium was changed the next day to remove Y27632.Continuous induction was performed until day 28 to obtain DAPs.Results Human iPSCs expressed the pluripotency markers OCT4,SOX2,Nanog,and SSEA1 and were positive for alkaline phosphatase staining.The hiPSCs-NECs were obtained on day 13 in the form of neural rosettes expressing neuroepithelial markers SOX2,nestin,and PAX6.In digested hiPSCs-NECs,the addition of 5 μmol/L Y27632 significantly promoted survival of the adherent cells,increased cell viability and the proportion of S-phase cells(P<0.01),and reduced the rate of apoptotic cells(P<0.05).On day 28 of induction,the obtained cells highly expressed the specific markers of DAPS(TH,FOXA2,NURR1,and Tuj1).Conclusion Treatment with Y27632(5 μmol/L)for 24 h significantly promotes the survival of human iPSCs-NECs during their differentiation into DPAs without affecting the cell differentiation,which indirectly enhances the efficiency of cell differentiation.
6.Rho kinase inhibitor Y27632 promotes survival of human induced pluripotent stem cells during differentiation into functional midbrain dopaminergic progenitor cells in vitro
Yangyang LI ; Jiajia XU ; Chengcheng JIANG ; Zilong CHEN ; Ying CHEN ; Mengjiao YING ; Ao WANG ; Caiyun MA ; Chunjing WANG ; Yu GUO ; Changqing LIU
Journal of Southern Medical University 2024;44(2):236-243
Objective To improve the efficiency of induced differentiation of primitive neural epithelial cells derived from human induced pluripotent stem cells(hiPSCs-NECs)into functional midbrain dopaminergic progenitor cells(DAPs).Methods HiPSCs were cultured in mTeSRTM medium containing DMH1(10 μmol/L),SB431542(10 μmol/L),SHH(200 ng/mL),FGF8(100 ng/mL),purmorphamine(2 μmol/L),CHIR99021(3 μmol/L),and N2(1%)for 12 days to induce their differentiation into primitive neuroepithelial cells(NECs).The hiPSCs-NECs were digested with collagenase IV and then cultured in neurobasal medium supplemented with 1%N2,2%B27-A,BDNF(10 ng/mL),GDNF(10 ng/mL),AA,TGF-β,cAMP,and 1%GlutaMax in the presence of different concentrations of Rho kinase inhibitor Y27632,and the culture medium was changed the next day to remove Y27632.Continuous induction was performed until day 28 to obtain DAPs.Results Human iPSCs expressed the pluripotency markers OCT4,SOX2,Nanog,and SSEA1 and were positive for alkaline phosphatase staining.The hiPSCs-NECs were obtained on day 13 in the form of neural rosettes expressing neuroepithelial markers SOX2,nestin,and PAX6.In digested hiPSCs-NECs,the addition of 5 μmol/L Y27632 significantly promoted survival of the adherent cells,increased cell viability and the proportion of S-phase cells(P<0.01),and reduced the rate of apoptotic cells(P<0.05).On day 28 of induction,the obtained cells highly expressed the specific markers of DAPS(TH,FOXA2,NURR1,and Tuj1).Conclusion Treatment with Y27632(5 μmol/L)for 24 h significantly promotes the survival of human iPSCs-NECs during their differentiation into DPAs without affecting the cell differentiation,which indirectly enhances the efficiency of cell differentiation.
7.Prognostic value of metabolic parameters on 18F-FDG PET/CT imaging and clinical features in patients with squamous cell carcinoma of the cervix
Yangyang WANG ; Guangjie YANG ; Wenlong YAN ; Jie MA ; Lei YAN ; Yanli DUAN ; Lianshuang XIA ; Yan KONG ; Yashuo YU ; Zhenguang WANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(8):462-467
Objective:To estimate the influence of metabolic parameters in 18F-FDG PET/CT and clinically relevant indicators on the prognosis of patients with cervical cancer. Methods:A total of 174 patients with cervical cancer (age (53.6±11.1) years) who underwent baseline 18F-FDG PET/CT examination in the Affiliated Hospital of Qingdao University from May 2011 to December 2020 were retrospectively collected. Metabolic parameters (metabolic tumor volume of primary lesion (MTV p), total lesion glycolysis of primary lesion (TLG p), MTV sum of total lesions (MTV total) in the whole body, TLG sum of total lesions (TLG total)) and clinical parameters (International Federation of Gynecology and Obstetrics (FIGO) stage, tumor maximum diameter ( Dmax), et al) were collected. Cox regression and Kaplan-Meier method were performed to evaluate the prognostic and predictive values of those parameters. Results:The follow-up time was 6-120 months, during which 52 patients (29.9%, 52/174) developed progression. The 5-year overall survival (OS), progression-free survival (PFS), local control (LC) and distant metastasis-free survival (DMFS) rates were 83.3%(145/174), 70.1%(122/174), 75.3%(131/174) and 82.8%(144/174), respectively. Cox regression showed that FIGO stage and MTV total were independent factors for predicting PFS, OS and LC (hazard ratio ( HR): 1.005-11.605, all P<0.05). FIGO stage and TLG total were independent factors for predicting DMFS ( HR: 1.002-12.258, all P<0.05). Conclusion:MTV total and FIGO stage are effective predictors of patients with cervical squamous cell carcinoma.
8.Association between gestational weight gain in twin pregnancies with adverse perinatal outcomes
Yangyang LI ; Jie LIU ; Lin HOU ; Zijun MA ; Chaomei ZENG ; Jiong QIN ; Yanqiu WU
Chinese Journal of Perinatal Medicine 2024;27(8):617-623
Objective:To investigate the relationship between gestational weight gain (GWG) in twin pregnancies and adverse perinatal outcomes.Methods:This retrospective study included twin pregnant women with live births at≥25 weeks of gestation and their offspring, who delivered at Peking University People's Hospital from January 2012 to October 2022. Total GWG was standardized according to gestational age and categorized into three groups based on the 2009 Institute of Medicine (IOM) guidelines: insufficient GWG (GWG below IOM recommendations), appropriate GWG (GWG within IOM recommendations), and excessive GWG (GWG above IOM recommendations). Comparisons between data of the three groups used analysis of variance, Kruskal-Wallis test or Bonferroni correction or Chi-square partitions. Multivariable logistic regression models and generalized estimating equations with logistic regression models were used to analyze the independent effects of GWG on maternal and neonatal outcomes. Results:A total of 794 twin pregnant women and their 1 588 live-born neonates were included in the study. There were 360 women (45.3%) with appropriate GWG, 356 (44.8%) with insufficient GWG, and 78 (9.8%) with excessive GWG. Both insufficient and excessive GWG were associated with an increased risk of preterm birth [adjusted ORs of 1.39 (95% CI: 1.04-1.88) and 1.70 (95% CI: 1.05-2.78), respectively]. Insufficient GWG was associated with an increased risk of gestational diabetes mellitus (adjusted OR=1.42, 95% CI: 1.00-2.01) and low birth weight infants (adjusted OR=2.04, 95% CI: 1.57-2.66). Insufficient GWG was also associated with a reduced risk of eclampsia or preeclampsia (adjusted OR=0.50, 95% CI: 0.33-0.75), cesarean section (adjusted OR=0.48, 95% CI: 0.30-0.77), discordant twin growth (adjusted OR=0.56, 95% CI: 0.37-0.85), and large for gestational age infants (adjusted OR=0.46, 95% CI: 0.35-0.61). Excessive GWG was associated with an increased risk of eclampsia or preeclampsia (adjusted OR=2.85, 95% CI: 1.65-4.91), and large for gestational age infants (adjusted OR=2.49, 95% CI: 1.60-3.86), while with a decreased risk of low birth weight infants (adjusted OR=0.42, 95% CI: 0.27-0.65). Conclusions:More than half of the twin pregnancies have GWG outside the recommended range of the IOM guidelines. Both insufficient and excessive GWG are associated with adverse perinatal outcomes, particularly an increased risk of preterm birth.
9.The effect of recombinant human prourokinase on without reflow or slow blood flow during emergency percutaneous coronary intervention in patients with acute inferior ST segment elevation myocardial infarction
Fang WANG ; Long MA ; Yangyang HE ; Hao FENG ; Xiaotong ZHU ; Hui YONG
China Modern Doctor 2024;62(30):79-82
Objective To explore the clinical efficacy of recombinant human prourokinase during emergency coronary intervention (PCI) in patients with acute inferior wall ST segment elevation myocardial infarction (STEMI) without reflow or slow blood flow.Methods Eighty patients with acute inferior wall STEMI admitted to Xinyi People's Hospital from January 2022 to December 2023 were selected.The patients were divided into two groups,40 cases in each group.The control group patients accepted PCI after receiving 100μg nitroglycerin or nitroprusside via catheter;On the basis of control group,the observation group patients received 20mg recombinant human prourokinase via catheter until infarct related artery,and PCI was performed.Using thrombolysis in myocardial infarction (TIMI) blood flow grading method,compared the immediate myocardial perfusion after surgery.Results Comparison of immediate TIMI blood flow grading between two groups of patients during surgery,with grades ranging from level 0 to 1:1 case (2.5%) in observation group and 7 cases (17.5%) in control group.The difference between two groups was statistically significant (P<0.05);Level 2:3 cases (7.5%) in observation group and 8 cases (20.0%) in control group.There was no statistically significant difference between two groups (P>0.05);Level 3:36 cases (90.0%) in observation group and 25 cases (62.5%) in control group.The difference between two groups was statistically significant (P<0.05).Conclusion Recombinant human prourokinase can effectively improve the coronary blood flow of infarct related artery during emergency PCI in patients with acute inferior wall STEMI,improve myocardial ischemia,and do not increase adverse reactions such as bleeding,which is of great significance for improving patient's prognosis.
10.Research progress of fatigue in patients with cirrhosis
Yujuan LIU ; Xiaodan ZHANG ; Ying YI ; Xueyao MA ; Juan MAO ; Yangyang DING ; Lingling DUAN
Chinese Journal of Practical Nursing 2024;40(24):1917-1921
Fatigue is one of the common symptoms in patients with liver cirrhosis, which has a serious impact on the quality of life of patients. This article reviews the influencing factors and intervention strategies of fatigue in patients with cirrhosis, aiming to provide reference for early recognition and intervention of fatigue in patients with cirrhosis.


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