1.Mechanism of Cistanche phenylethanoid glycosides in treating osteoporosis by regulating osteogenic differentiation via SIRT2-C/EBPβ-AREG axis
Yue ZHANG ; Lizi YE ; Leiming LUO ; Yuanhui WANG ; Zhi WANG ; Zhong LI
Journal of China Medical University 2025;54(11):1011-1016,1022
Objective To explore the mechanism of Cistanche phenylethanoid glycosides(CPhGs)in treating osteoporosis by regu-lating osteogenic differentiation via SIRT2-C/EBPβ-AREG axis.Methods An osteoporosis mouse model was established using ova-riectomy.Trabecular number/thickness,bone formation rate,and tissue morphology were evaluated using micro-computed tomography,calcein double labeling,and hematoxylin and eosin staining,respectively.SIRT2,C/EBPβ,AREG,proteins related to the SIRT2-C/EBPβ-AREG axis,were analyzed by Western blotting and co-immunoprecipitation.The mRNA expression of osteogenic differentiation marker genes OCN,OPN,RUNX2,C/EBPβ,and AREG were detected by real-time quantitative PCR.Results CPhGs intervention significantly improved the trabecular microarchitecture and promoted bone formation in mice undergoing ovariectomy,and the mechanism involved the activation of SIRT2-mediated deacetylation of C/EBPβ,which in turn upregulated AREG expression.Cell experiments confirmed that CPhGs significantly increased the activity of alkaline phosphatase and the expression of osteogenic genes such as OCN,OPN,and RUNX2 in MC3T3-E1 cells by enhancing the interaction between SIRT2 and C/EBPβ.Notably,this effect could be reversed by SIRT2 knockdown.Conclusion CPhGs regulate the osteogenic differentiation process through the SIRT2-C/EBPβ-AREG axis,providing a new molecular target and theoretical basis for the treatment of osteoporosis with the active ingredients of traditional Chinese medicine.
2.Mechanism of Cistanche phenylethanoid glycosides in treating osteoporosis by regulating osteogenic differentiation via SIRT2-C/EBPβ-AREG axis
Yue ZHANG ; Lizi YE ; Leiming LUO ; Yuanhui WANG ; Zhi WANG ; Zhong LI
Journal of China Medical University 2025;54(11):1011-1016,1022
Objective To explore the mechanism of Cistanche phenylethanoid glycosides(CPhGs)in treating osteoporosis by regu-lating osteogenic differentiation via SIRT2-C/EBPβ-AREG axis.Methods An osteoporosis mouse model was established using ova-riectomy.Trabecular number/thickness,bone formation rate,and tissue morphology were evaluated using micro-computed tomography,calcein double labeling,and hematoxylin and eosin staining,respectively.SIRT2,C/EBPβ,AREG,proteins related to the SIRT2-C/EBPβ-AREG axis,were analyzed by Western blotting and co-immunoprecipitation.The mRNA expression of osteogenic differentiation marker genes OCN,OPN,RUNX2,C/EBPβ,and AREG were detected by real-time quantitative PCR.Results CPhGs intervention significantly improved the trabecular microarchitecture and promoted bone formation in mice undergoing ovariectomy,and the mechanism involved the activation of SIRT2-mediated deacetylation of C/EBPβ,which in turn upregulated AREG expression.Cell experiments confirmed that CPhGs significantly increased the activity of alkaline phosphatase and the expression of osteogenic genes such as OCN,OPN,and RUNX2 in MC3T3-E1 cells by enhancing the interaction between SIRT2 and C/EBPβ.Notably,this effect could be reversed by SIRT2 knockdown.Conclusion CPhGs regulate the osteogenic differentiation process through the SIRT2-C/EBPβ-AREG axis,providing a new molecular target and theoretical basis for the treatment of osteoporosis with the active ingredients of traditional Chinese medicine.
3.Clinicopathological characteristics of gangliogliomas with anaplastic morphology
Linai GUO ; Leiming WANG ; Yongjuan FU ; Tao LUO ; Xiaotong FAN ; Lihong ZHAO ; Xiaohong YAO ; Yueshan PIAO
Chinese Journal of Pathology 2024;53(6):585-591
Objective:To investigate the clinical, radiological, and pathological features of anaplastic gangliogliomas (AGGs) and to determine whether these tumors represent a distinct entity.Methods:Consecutive 667 cases of ganglioglioma (GG) diagnosed at the Xuanwu Hospital, Capital Medical University, Beijing, China between January 2015 and July 2023 were screened. Among these cases, 9 pathologically confirmed AGG cases were identified. Their clinical, radiological, treatment, and outcome data were analyzed retrospectively. Most of the tumor samples were subject to next-generation sequencing, while a subset of them were subject to DNA methylation profiling.Results:Among the 9 patients, there were five males and four females, with a median age of 8 years. Epileptic seizures (5/9) were the most frequently presented symptom. Radiological examinations showed three types of radiological manifestations: four cases showed abnormal MRI signals with no significant mass effects and mild enhancement; two cases demonstrated a mixed solid-cystic density lesion with peritumoral edema, which showed significant heterogeneous enhancement and obvious mass effects, and one case displayed cystic cavity formation with nodules on MRI, which showed evident enhancements. All cases exhibited mutations that were predicted to activate the MAP kinase signaling pathway, including seven with BRAF p.V600E mutation and two with NF1 mutation. Five AGGs with mutations involving the MAP kinase signaling pathway also had concurrent mutations, including three with CDKN2A homozygous deletion, one with a TERT promoter mutation, one with a H3F3A mutation, and one with a PTEN mutation.Conclusions:AGG exhibits a distinct spectrum of pathology, genetic mutations and clinical behaviors, differing from GG. Given these characteristics suggest that AGG may be a distinct tumor type, further expansion of the case series is needed. Therefore, a comprehensive integration of clinical, histological, and molecular analyses is required to correctly diagnose AGG. It will also help guide treatments and prognostication.
4.Effects of contrast-induced nephropathy and perioperative myocardial injury on short-term prognosis in patients after percutaneous coronary intervention
Yulong LI ; Shaopan ZHAO ; Shihui FU ; Leiming LUO
Adverse Drug Reactions Journal 2021;23(4):178-183
Objective:To investigate the effects of contrast-induced nephropathy (CIN) and/or perioperative myocardial injury (PMI) on the short-term prognosis of patients after percutaneous coronary intervention (PCI).Method:The study was designed as a prospective cohort study. The subjects were selected from patients with acute coronary syndrome (ACS) who underwent PCI in the Department of Cardiology, the First Medical Center, General Hospital of Chinese people′s Liberation Army from August to October 2015. According to the occurrence of CIN and PMI after operation, the patients were divided into 4 groups: no injury group, CIN group, PMI group, and CIN+PMI group. The patients were followed up for 12 months, and the end point was the main adverse cardiovascular events (MACE). The differences in basic characteristics (sex, age, ACS type, underlying diseases, past medical history, etc.), the preoperative levels of serum creatinine, triglyceride, low density lipoprotein cholesterol, fasting blood glucose, high sensitivity troponin T (hs-cTnT), creatine kinase (CK) MB, C-reactive protein, and N terminal pro-B type natriuretic peptide (NT-proBNP), levels of serum creatinine, hs-cTnT, CK-MB, and NT-proBNP within 48 hours after operation, and the occurrence of MACE were compared in patients among the 4 groups. The effects of CIN and/or PMI on the occurrence of MACE within 12 months after operation were analyzed using COX multivariate regression model.Results:A total of 299 patients were included in the cohort study, including 216 males (72.2%) and 83 females (27.8%), with an average age of 60 years (range, 26-84 years). Of them, 125 patients (41.8%) were with ST segment elevation myocardial infarction (STEMI). One hundred and eighty-two patients (60.9%), 18 patients (6.0%), 79 patients (26.4%), and 20 patients (6.7%) were included in the non-injury group, CIN group, PMI group, and CIN+PMI group, respectively. The incidence of CIN in all patients was 12.7% (38/299) and that of PMI was 33.1% (99/299). No subjects were lost during the 12-month follow-up. Of the 299 patients, 24 subjects had 26 times of MACE [cardiogenic death, nonfatal myocardial infarction (NF-MI), target vessel revascularization (TVR), and stroke occurred 3, 5, 5, and 13 times, respectively] and the incidence of MACE was 8.0%. The incidences of MACE in the no injury group, CIN group, PMI group, and CIN+PMI group were 1.6% (3/182), 11.1% (2/18), 11.4% (9/79), and 50.0% (10/20), respectively, and the difference among groups was statistically significant ( P<0.001). The results of COX multivariate regression analysis showed increased risk of MACE in the other 3 groups [hazard risk ( HR)=6.897, 95%confidence interval ( CI): 1.152-41.281, P=0.034; HR=7.623,95 %CI: 2.063-28.167, P=0.002; HR=43.087, 95 %CI: 11.817-157.098, P<0.001) compared with the non-injury group. Conclusion:Both CIN and PMI can increase the risk of MACE in patients within 12 months after PCI treatment, which can be further increased in the coexistence of them.
5.Effects of contrast-induced nephropathy and perioperative myocardial injury on short-term prognosis in patients after percutaneous coronary intervention
Yulong LI ; Shaopan ZHAO ; Shihui FU ; Leiming LUO
Adverse Drug Reactions Journal 2021;23(4):178-183
Objective:To investigate the effects of contrast-induced nephropathy (CIN) and/or perioperative myocardial injury (PMI) on the short-term prognosis of patients after percutaneous coronary intervention (PCI).Method:The study was designed as a prospective cohort study. The subjects were selected from patients with acute coronary syndrome (ACS) who underwent PCI in the Department of Cardiology, the First Medical Center, General Hospital of Chinese people′s Liberation Army from August to October 2015. According to the occurrence of CIN and PMI after operation, the patients were divided into 4 groups: no injury group, CIN group, PMI group, and CIN+PMI group. The patients were followed up for 12 months, and the end point was the main adverse cardiovascular events (MACE). The differences in basic characteristics (sex, age, ACS type, underlying diseases, past medical history, etc.), the preoperative levels of serum creatinine, triglyceride, low density lipoprotein cholesterol, fasting blood glucose, high sensitivity troponin T (hs-cTnT), creatine kinase (CK) MB, C-reactive protein, and N terminal pro-B type natriuretic peptide (NT-proBNP), levels of serum creatinine, hs-cTnT, CK-MB, and NT-proBNP within 48 hours after operation, and the occurrence of MACE were compared in patients among the 4 groups. The effects of CIN and/or PMI on the occurrence of MACE within 12 months after operation were analyzed using COX multivariate regression model.Results:A total of 299 patients were included in the cohort study, including 216 males (72.2%) and 83 females (27.8%), with an average age of 60 years (range, 26-84 years). Of them, 125 patients (41.8%) were with ST segment elevation myocardial infarction (STEMI). One hundred and eighty-two patients (60.9%), 18 patients (6.0%), 79 patients (26.4%), and 20 patients (6.7%) were included in the non-injury group, CIN group, PMI group, and CIN+PMI group, respectively. The incidence of CIN in all patients was 12.7% (38/299) and that of PMI was 33.1% (99/299). No subjects were lost during the 12-month follow-up. Of the 299 patients, 24 subjects had 26 times of MACE [cardiogenic death, nonfatal myocardial infarction (NF-MI), target vessel revascularization (TVR), and stroke occurred 3, 5, 5, and 13 times, respectively] and the incidence of MACE was 8.0%. The incidences of MACE in the no injury group, CIN group, PMI group, and CIN+PMI group were 1.6% (3/182), 11.1% (2/18), 11.4% (9/79), and 50.0% (10/20), respectively, and the difference among groups was statistically significant ( P<0.001). The results of COX multivariate regression analysis showed increased risk of MACE in the other 3 groups [hazard risk ( HR)=6.897, 95%confidence interval ( CI): 1.152-41.281, P=0.034; HR=7.623,95 %CI: 2.063-28.167, P=0.002; HR=43.087, 95 %CI: 11.817-157.098, P<0.001) compared with the non-injury group. Conclusion:Both CIN and PMI can increase the risk of MACE in patients within 12 months after PCI treatment, which can be further increased in the coexistence of them.
6.Effect of pioglitazone on expression of p38 mitogen-activated protein kinase in myocardium of rats following I/R injury
Hao WANG ; Ping YE ; Qiwei ZHU ; Leiming LUO
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2018;20(2):188-190
Objective To study the effect of pioglitazone,a member of the thiazolidinedione (TZD) class with hypoglycemic action to treat diabetes,on expression of p38 mitogen-activated protein kinase in myocardium of rats following I/R injury.Methods Twenty-four healthy SD rats were randomly divided into sham group,I/R injury group,pioglitazone treatment group and pioglitazone+peroxisome proliferator-activated receptors-γ specific antagonist GW9662 treatment group (6 in each group).A rat I/R injury model was established by ligating the left anterior descending coronary artery.Apoptosis of myocardial cells was assayed by Terminal dUTP deoxynucleotidyl transferase nick end labeling.Expression of p-p38 protein was detected by Western blot.Results The apoptosis index of myocardial cells was significantly lower in sham operation group and piogl itazone treatment group than in I/R injury group and was significantly higher in pioglitazone+ GW9662 treatment group than in pioglitazone treatment group (8.6%±4.3%,21.4%±8.8% vs 40.1%±12.3%,P<0.05;37.0%-10.5% vs 21.4%±8.8%,P<0.05).The expression level of p-p38 was significantly lower in sham operation group and pioglitazone treatment group than in I/R injury group and was significantly higher in pioglitazone+GW9662 treatment group than in pioglitazone treatment group (P<0.05).Conclusion Pioglitazone can inhibit I/R injury-induced apoptosis of myocardial cells by downregulating the expression of p-p38 protein.
7.Effects of sleep situation on circadian rhythm of blood pressure in elderly patients with hypertension
Shaopan ZHAO ; Shihui FU ; Leiming LUO
Chinese Journal of Geriatrics 2018;37(4):405-408
Objective To explore the effects of sleep situation on circadian rhythm of blood pressure in elderly hypertension patients.Methods Two hundred and thirty patients (aged ≥ 60 years) with hypertension treated in the Department of Geriatric Cardiology of PLA General Hospital were enrolled in the study from October 2016 to December 2016.After admission,the clinical and laboratory tests data and examinations of the patients were collected and analyzed.The patients' sleep was investigated by Pittsburgh sleep quality index (PSQI).The ambulatory blood pressure rhythm was divided into three groups:reverse-dipper group (n=110),non-dipper group (n=86),and dipper group (n=34).The clinical data and sleep situation of different blood pressure rhythm groups were compared,and the effects of sleep situation on different blood pressure rhythm were analyzed.Results The total PSQI score with six domains[P<0.01,except hypnotic drug (P>0.05)]was significantly lower in dipper group than in reverse-and non-dipper group.The sleep situation was significantly better in dipper group than in reverse-and non-dipper group (P<0.05).Multiple linear regression analysis showed a significant negative correlation between total PSQI score and nocturnal blood pressure drop after adjusting for risk factors of hypertension (β =-0.651,P <0.01).Furthermore,after further adjusting for the seven domains of the PSQI score,the negative correlation remained between the sleep time score and the nocturnal blood pressure drop (β=-1.926,P =0.031).The elderly hypertension patients with shorter sleep duration had a lower rate of nocturnal blood pressure decline,and were prone to present the reverse-dipper and non-dipper blood pressure rhythm.Conclusions The elderly hypertension patients with poor sleep quality,especially with short sleep duration,are prone to present the reverse-dipper and non-dipper blood pressure rhythm.Short sleep duration can be used as a predictor for abnormal blood pressure rhythm.
8.Association between NT-proBNP and elevated nocturnal blood pressure in male elderly primary hypertension patients
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2017;19(8):833-836
Objective To study the association between NT-proBNP and elevated nocturnal blood pressure in male elderly primary hypertension patients.Methods Five hundred and ninety male elderly primary hypertension patients,admitted to our hospital from January 2009 to December 2012,were divided into non dipper hypertensivon group (n=418) and anti-dipper hypertension group (n =172).Their clinical data,laboratory test parameters and ambulatory ECG findings were recorded.Results The age was older,the serum levels of creatinine,HbAlc and NT-proBNP were higher in anti-dipper hypertension group than in non-dipper hypertensivon group (81.47± 9.25 years vs 77.81±11.10 years,P=0.000;113.18±99.70 μmol/L vs 93.35±84.49 μmol/L,P=0.017;7.34%±8.35% vs 6.37%±1.05%,P=0.001;551.16±991.72 ng/L vs 355.12±934.89 ng/L,P=0.009).Multivariate regression analysis showed that average day systolic blood pressure was independently associated with NT-proBNP (P=0.004).Conclusion The loss of rhythmia is more noticeable and the target organ damage is more serious in anti-dipper hypertension patients than in non-dipper hypertensivon patients.The serum NT-proBNP level plays a certain role in regulating blood pressure.
9.Urine albumin excretion and related factors in patients with essential hypertension
Minghua ZHANG ; Ping YE ; Leiming LUO ; Wenkai XIAO ; Hongmei WU ; Dejun LIU ; Guoshu LIU
Chinese Journal of cardiovascular Rehabilitation Medicine 2016;25(1):28-32
Objective:To study urine albumin excretion (UAE) and its related factors in patients with essential hyper‐tension (EH) .Methods :A total of 113 EH patients without significant target organ damage were enrolled as EH group ,while another 92 healthy subjects were regarded as healthy control group .Ratio of morning urinary albumin to creatinine was measured and regarded as UAE index .Plasma homocysteine (Hcy) ,serum uric acid ,creatinine , blood urea nitrogen ,blood glucose ,blood lipids etc .levels were measured ,and compared between two groups Re‐sults:Compared with healthy control group ,there were significant rise in UAE ,body mass index (BMI) ,waist hip ratio ,blood pressure ,pulse pressure ,heart rate ,plasma levels of triglyceride (TG) ,low density lipoprotein choles‐terol (LDL‐C) ,serum uric acid and Hcy (P<0.05 or <0.01) ,and significant reduction in level of high density lip‐oprotein cholesterol (HDL‐C) in EH group ( P=0.001) .Pearson correlation analysis indicated that lgUAE was pos‐itively correlated with lgTG (r=0.257 ,P=0.015) and estimated glomerular filtration rate (eGFR ,r=0.284 ,P=0.007) ,and inversely correlated with lg creatinine (r= -0.277 ,P=0.008) in healthy control group ,while in EH group ,lgUAE was positively correlated BMI (r=0.231 ,P=0.014) ,lgTG (r=0.200 ,P=0.034) and lgHcy (r=0.244 , P=0.009) .Muti-factor gradual regression analysis indicated that lg TG (β=0.265 ,P=0.001) and lg Hcy (β=0.170 , P=0.012) were independently positively correlated with lg UAE , R2 =0.112.Conclusion:UAE level significantly rises in EH patients ,and it′s significantly positively correlated with plasma levels of TG and Hcy .
10.Comparison of two methods for treating adult humeral shaft fracture
Yongxian WAN ; Lili XU ; Yuanhui WANG ; Leiming LUO ; Xiaobo LU
Chongqing Medicine 2016;45(19):2626-2628,2631
Objective To evaluate the clinical effects of open reduction plate screw nail internal fixed and minimally invasive elastic intramedullary nail internal fixation combined with neck strap suspension for treating adult humeral shaft fracture . Methods A retrospective analysis was made on the clinical data of 65 patients with humeral shaft fracture in our hospital from March 2012 to March 2014 ,including 38 cases of open reduction plate screw internal fixation (plate screw nail fixation group) and 27 cases of limited open or closed reduction elastic intramedullary nail internal fixation combined with neck strap suspension (elastic intramedullary nail group) .The operation time ,intraoperative blood loss amount ,iatrogenic radial nerve injury ,occurrence rate of incision infection ,postoperative fracture reduction degree ,fracture recovery time and elbow joint function score were compared be‐tween the two groups .Results The operation time and intraoperative bleeding volume in the elastic intramedullary nail group were less than those in the plate screw nail fixation group ,the differences were statistically significant (P<0 .05);the postoperative frac‐ture healing rate had no statistically significant difference between the two groups (P>0 .05) ,the postoperative shoulder and elbow joint function scores in the plate screw nail group were significantly higher than those in the elastic intramedullary nail group ,the difference was statistically significant (P<0 .05) .No serious nerve damage ,incision infection and other postoperative complications occurred in the two groups .Conclusion Both the open reduction plate screw nail internal fixation and elastic intramedullary nail in‐ternal fixation are effective method for treating adult humeral shaft fracture ,the latter has shorter operation time ,less intraoperative bleeding ,but shoulder elbow pain and limitation of motion are more serious than the former .

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