1.EDA mutation screening and phenotype analysis in patients with tooth agenesis
Huiying HE ; Yang LIU ; Dong HAN ; Haochen LIU ; Baojing BAI ; Hailan FENG
Journal of Peking University(Health Sciences) 2016;48(4):686-691
Objective:To screen the ectodysplasin A (EDA)gene mutation in the patients with non-syndromic tooth agenesis and ectodermal dysplasia,and to analyze the phenotype of missing teeth pattern in these two groups of patients.Methods:In the study,174 patients with tooth agenesis (143:non-syn-dromic,31:ectodermal dysplasia)and 451 health control volunteers were enrolled from the clinic,and the genome DNA was extracted from either peripheral blood or oral mucosal swab.The coding region of EDA gene was then amplified by PCR,sequenced and blasted to online NCBI database.The missing teeth were recorded for all patients,and the missing teeth from patients with EDA mutation were com-pared among the different dentition sites.Results:33 patients were identified with EDA mutation.In the non-syndromic patients,13 /143(9.09%)were identified with EDA mutation,while in patients with ec-todermal dysplasia,20 /31 (64.52%)were found with EDA mutation.Ten novel EDA mutations were identified (c.769G >C[p.G257R],c.936C >G[p.I312M],c.223G >A[p.E75K],c.1166C >T[p. P389L],c.133G >C[p.G45R],c.1109G >A[p.E370K],c.914G >T[p.S305I],c.916C >T[p. Q306X],c.602G >T[p.G201V],c.88 -89insG[p.A30GfsX69]).For each dentition site there was no statistic difference in the number of missing teeth between the left and right sides,so the number from both sides were combined later in the analysis.In the patients with EDA mutation,the non-syndromic pa-tients had fewer missing teeth (15.9 ±6.4 missing teeth for each,207 /364 in total)than the patients with ectodermal dysplasia (23.9 ±4.3,478 /560).In the non-syndromic patients with EDA mutation, the maxillay central incisors and first molars were less affected,with the same missing rate as 19.2% (5 /26).While the mandibular central incisors (with a missing rate of 76.9%,20 /26),the maxillary late-ral incisors (the missing rate:88.5%,23 /26 ),the mandibular lateral incisors (the missing rate:80.8%,21 /26),and the maxillary first premolars (the missing rate:80.8%,21 /26)were more likely to be missing.In the ectodermal dysplasia patients with EDA mutation,only maxillary central incisors (the missing rate:60%,24 /40),maxillary canines (the missing rate:70%,28 /40),mandibular ca-nines (the missing rate:67.5%,27 /40),maxillary first molars (the missing rate:65%,26 /40)and mandibular first molars (the missing rate:72.5%,29 /40)had higher possibility of persistence.Teeth at other dentition sites were more likely to be affected (the minimum missing rate:87.5%,35 /40). Conclusion:The findings would help to reveal the EDA gene and its function in ectodermal organogene-sis.
2.Effects of HBV co-infection on liver function of patientswith different types of hepatic echinococcosis
Runchen MIAO ; Haining FAN ; Yongshou LI ; Zhixin WANG ; Lingqiang ZHANG ; Yanyan ZHOU ; Haochen LIU ; Chang LIU
Journal of Xi'an Jiaotong University(Medical Sciences) 2017;38(5):725-729
Objective To clarify the effects of HBV co-infection on liver function of patients with different types of hepatic echinococcosis.Methods We recruited 409 patients diagnosed with hepatic echinococcosis at three hospitals in western regions in China from 2014 to 2015.Venous blood was withdrawn to detect to liver function indications.ELISA was performed to detect HBsAg.We analyzed liver function in patients stratified by different types of hepatic echinococcosis with or without HBV infection.Results The hepatic echinococcosis patients infected with HBV had more severe impairment in liver functions such as reduced albumin and increased transaminase.The patients with hepatic alveolar echinococcosis were more vulnerable to HBV infection compared with those with hepatic cystic echinococcosis (38.4% vs.86.4%, P<0.05).In addition, liver injury was more severe in patients diagnosed with alveolar hepatic echinococcosis and HBV infection compared with those diagnosed with cystic hepatic echinococcosis and HBV infection (all P<0.05).Conclusion Hepatic alveolar echinococcosis patients co-infected with HBV have worse liver injury compared with those hepatic cystic with HBV. Therefore, they deserve special attention in clinical treatment.
3.Effect of phentolamine on N terminal B-type natriuretic peptide precursor,blood gas analysis,hypersensitive c-reactive protein and plasma D-dimer in patients with chronic cor pulmonale
Xiaoqing HAN ; Yuchen JIANG ; Baoquan XIE ; Tienan LIU ; Chuntao WU ; Lirui LI ; Chao HUANG ; Lingling HU ; Haochen WANG ; Hongyang WANG
Clinical Medicine of China 2017;33(4):292-295
Objective To observe the influence of phentolamine on N terminal B-type natriuretic peptide precursor(NT-proBNP),blood gas analysis,hypersensitive c-reactive protein and plasma D-dimer in patients with chronic cor pulmonale Methods One hundred and one cases patients with chronic cor pulmonale were randomly divided into two groups,51 patients in the treatment group,50 patients in the control group.All patients were treated with normal anti-infection,eliminating phlegm to smooth wheezing antithrombotic for one week,as the same time patients in the treatment group were treated with phentolamine for one week.Through observed the treatment effect of phentolamine to chronic cor pulmonale,the level of NT-proBNP,blood gas analysis,hypersensitive c-reactive protein and plasma D-dimer in patients with chronic cor pulmonale before and after the treatment were analyzed.Results Compared with before treatment,the levels of NT-proBNP,PCO2,hypersensitive c-reactive protein,plasma D dimer were lower than after one week in two groups,while the level of PO2 was higher.Treatment group:NT-proBNP (1 712.76±572.32) ng/L vs.(271.59±163.05) ng/L,t=20.42,P<0.05,PCO2 (66.34±5.81) mmHg vs.(52.58±5.82) mmHg,t=16.46,P<0.05,PO2 (59.28±6.13) mmHg vs.(73.64±6.10) mmHg,t=23.02,P<0.05,hypersensitive c-reactive protein 86.0(28.0) mg/L vs.23.0(12.0) mg/L,Z=-6.22,P<0.05 mg/L,plasma D-dimer (4 953.37±1 654.09) μg/L vs.(1 847.90±838.66) μg/L,t=17.11,P<0.05.Control group:NT-proBNP (1 527.24±658.70) ng/L vs.(612.58±357.59) ng/L,t=14.52,P<0.05,PCO2 (65.41±5.23) mmHg vs.(56.46±5.65) mmHg,t=13.04,P<0.05,PO2(60.57±5.84) mmHg vs.(67.21±5.19) mmHg,t=-10.06,P<0.05,hypersensitive c-reactive protein 79.0(29.0) mg/L vs.43.0(20.0) mg/L,Z=-6.16,,P<0.05,plasma D-dimer (4 408.02±1 682.83) μg/L vs.(2 598.28±1 242.73) μg/L,t=12.15,P<0.05.But the levels of NT-proBNP,PCO2,hypersensitive c-reactive protein and plasma D-dimer reduced significantly,the level of PO2 increased more significantly in treatment group(t(z)=-6.19,-3.39,-7.16,-3.56,5.70,all P<0.05).Conclusion Phentolamine can reduce the level of NT-proBNP,PCO2,hypersensitive c-reactive protein and plasma D-dimer and increased the level of PO2 in patients with chronic cor pulmonale.Phentolamine combined with routine treatment can improve the clinical efficacy of patients with chronic cor pulmonale.
4.Evaluating cerebral endothelial dysfunction induced by amyloid based on the time series model
Chengyan ZHU ; Haochen LIU ; Hua HE ; Xiaoquan LIU
Journal of China Pharmaceutical University 2018;49(4):456-462
Time series model was developed to investigate the effect and contributions of related biomarkers on the cerebral endothelial dysfunction induced by beta amyloid(Aβ). HCMEC/D3 was incubated with 2. 5 μmol/L Aβ for 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22 and 24 h, and biomarkers including cytosolic calcium ion, mitochondrial membrane potential(MMP), endothelial nitric oxide synthase(eNOS)and cell viability were determined. Time series model was established to assess the dynamic relationship between the related biomarkers and cell viability and the contribution of different biomarkers to cell damage. Impulse response analysis indicated that after a positive impact on cytosolic calcium ion, cell viability decreased and this impact continued to decline; after a positive impact on endothelial nitric oxide synthase and mitochondrial membrane potential, cell viability increases, which increased rapidly in the early stage, and the rate decreased in later stage. The result of variance decomposition showed that the cytosolic calcium ion played a major role in cerebral endothelial dysfunction induced by Aβ. Combined with the model study, it is concluded that the intervention on the level of cytosolic calcium ion at the early stage may be the possible way to slow the disease progression.
5.Dihydroergotamine ameliorates synaptic atrophy in Alzheimer’s disease states and its effect on cognitive function
Peipei CHEN ; Jie WEI ; Xiaoquan LIU ; Haochen LIU
Journal of China Pharmaceutical University 2023;54(4):501-510
Studies suggest that synaptic damage is closely associated with cognitive dysfunction, and lemur tyrosine kinase 1 (LMTK1) is a key kinase that affects synaptic growth. Dihydroergotamine (DHE) is an ergot alkaloid derivative with high biological activity, which could regulate cognition, memory processing and motor control.This study aims to investigate the effect of DHE on synapse atrophy and plasticity as well as cognition in Alzheimer’s disease (AD) model animals.SAMR1 mice were selected as control group (n = 12).SAMP8 mice were randomly divided into 3 groups (n = 12 for each group):AD group, DHE low-dose group and high-dose group.The DHE groups were injected DHE intraperitoneally daily for 8 weeks.Immunofluorescence experiments, Golgi staining experiment, electrophysiological experiment, Morris water maze experiment (MWM) and Western blot experiment were conducted to investigate the effect of DHE on synaptic morphology, synaptic plasticity, cognitive function as well as the phosphorylation level of LMTK1 downstream TBC1D9B in AD model mice.Subsequently, the LMTK1 silencing and overexpression cells were constructed.Immunofluorescence experiments were used to study the effect of DHE on synaptic length of nerve cell after LMTK1 silencing and overexpression.In the hippocampus of AD mice, the postsynaptic marker PSD95 was significantly increased after DHE administration, which suggested that DHE could increase the synaptic density. In Golgi staining experiment, synaptic atrophy was observed in the hippocampal of AD mice, which could be improved by high-dose DHE.Compared with normal mice, the long-term potentiation (LTP) level of AD model mice was significantly reduced (P < 0.000 1), DHE could increase LTP significantly.The MWM experiment further showed that DHE could improve cognitive function in AD mice.WB experiments showed that the level of P-LMTK1 in the hippocampus of AD mice increased significantly, and the level of downstream P-TBC1D9B decreased significantly after DHE administration.Cell immunofluorescence experiments in vitro had shown that DHE significantly improved synaptic atrophy in overexpressed C17.2 cells, while its improvement disappeared when LMTK1 was silenced. This research suggests DHE may improve synaptic atrophy and cognitive dysfunction in AD by targeting on LMTK1.
6.Evaluation of cardiotoxicity of doxorubicin in rat by a novel metabolic balance model
Huiyong JIANG ; Yidan YAN ; Haochen LIU ; Yunsi ZHENG ; Yixuan WANG ; Hua HE ; Xiaoquan LIU
Journal of China Pharmaceutical University 2015;46(2):224-229
The study developed a metabolic balance model to evaluated the cardiotoxicity of doxorubicin. The rats were divided into 3 groups, control group(saline), low dose group(8 mg/kg of cumulative doxorubicin)and high dose group(15 mg/kg of cumulative doxorubicin). Doxorubicin or saline was intraperitoneally injected and blood sample was collected at day 1, 4, 7 and 10. The concentrations of nitric oxide(NO), B-type natriuretic peptide(BNP)and the activity of glutathion peroxidase(GSH-Px), xanthine oxidase(XOD)in rat plasma were determined. A metabolic balance model based on the four biomarkers was developed to evaluate the doxorubicin cardiotoxicity in rat. Doxorubicin leaded to significant changes of multiple biomarkers, resulting in metabolic balance disruption according to the metabolic balance maps and dynamic parameters of metabolic balance disruption. Moreover, the correlation study showed a good relationship between metabolic balance disruption and ejection fraction(EF). The metabolic balance model provide a novel method to integrally evaluate the doxorubicin-induced cardiotoxicity.
7.Application of VR and AR integrated teaching system in stomatology general medical education of clinical medicine students
Haochen GAO ; Xu HAN ; Qiang ZHU ; Qingjun JIANG ; Guoqin LIU ; Jiajun ZHOU ; Xing ZHENG ; Jianjin WU
Chinese Journal of Medical Education Research 2021;20(11):1279-1282
Objective:To investigate the application and effect of the virtual reality (VR) combined with the augmented reality (AR) integrated teaching system in stomatology general medical education of clinical medicine students.Methods:A total of 160 undergraduates from the five-year clinical medicine Batch 2015 of Naval Medical University were randomly divided into VR+AR group and traditional group, with 80 students in each group. A comparative analysis was made on the previous and teaching achievements of the two groups of students, and a questionnaire survey was conducted after the completion of the class. Epidata 3.0 was used to input questionnaire data, and SPSS 23.0 software was used to carry out t test, chi-square test and Fisher precision test. Results:There was no statistical difference in written test scores between the VR+AR group and the traditional group [(52.65±3.76) vs. (51.90±3.46), P=0.516], but the VR+AR group was significantly higher than the traditional group in case analysis scores [(35.85±2.56) vs. (31.40±2.96), P < 0.001] and overall performance [(88.50±4.95) vs. (83.30±4.86), P= 0.002]. The questionnaire survey results showed that the scores of "teaching mode" [(92.30±6.90) vs. (85.20±7.30), P<0.001], "teaching method" [(91.70±5.90) vs. (86.00±6.70), P=0.012] and "teaching improvement" [(90.70± 8.70) vs. (82.30±8.40), P<0.001] in VR + AR group were significantly higher than those in the traditional teaching group. Conclusion:The VR combined with AR integrated teaching system can significantly improve teaching performance and teaching quality, and is convenient for teaching demonstrations and simulation operations in small oral spaces, and is especially suitable for oral general medical education for clinical medicine.
8.Assessment of the Predictive Role of Serum Lipid Profiles in Breast Cancer Patients Receiving Neoadjuvant Chemotherapy
Fanli QU ; Rui CHEN ; Yang PENG ; Ying YE ; Zhenrong TANG ; Yihua WANG ; Beige ZONG ; Haochen YU ; Shengchun LIU
Journal of Breast Cancer 2020;23(3):246-258
Purpose:
Effective predictors of the response to neoadjuvant chemotherapy (NAC) are still insufficient. This study aimed to investigate the predictive value of serum lipid profiles for the response to NAC in breast cancer patients.
Methods:
A total of 533 breast cancer patients who had received NAC were retrospectively studied. The pretreatment of serum lipids, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and lipoprotein-α, and clinicopathological characteristics were collected to assess their predictive roles.
Results:
Breast cancer patients had significantly lower TC, TG, HDL-C, and LDL-C levels than normal individuals. Among these indicators, TG and LDL-C levels and HDL-C level increased and decreased significantly after NAC, respectively. In estrogen receptor (ER)-positive patients, increased LDL-C level was associated with better outcomes. Moreover, the receiver operating characteristic curve analyses suggested that TG and HDL-C levels at diagnosis can be used as predictors of the response to NAC only in the ER-positive subgroup.According to univariate analyses, patients with low TG level (< 1.155 mmol/L) or high HDL-C level (≥ 1.305 mmol/L) in the ER-positive subgroup had more favorable clinical responses than the other patients in the subgroup. Furthermore, according to multivariate analyses, a high HDL-C level (≥ 1.305 mmol/L, p = 0.007) was an independent predictor of NAC efficacy.
Conclusion
High HDL-C level (≥ 1.305 mmol/L) before NAC and increased LDL-C level after NAC were associated with the better treatment response in ER-positive breast cancer patients.These results are potentially considered beneficial in establishing treatment decisions.
9.Clinical features and prevention of dislocation after resection and reconstruction of tumors involving pelvic area II
Hao QU ; Haochen MOU ; Keyi WANG ; Cong WANG ; Hengyuan LI ; Xiumao LI ; Peng LIN ; Binghao LI ; Shengdong WANG ; Zhan WANG ; Meng LIU ; Xiaobo YAN ; Xin HUANG ; Yong LIN ; Zhaoming YE
Chinese Journal of Orthopaedics 2022;42(8):500-508
Objective:To explore the clinical characteristics of dislocation after resection and reconstruction of tumors involving pelvic area II, and to try to propose intraoperative and postoperative techniques to prevent its occurrence.Methods:From March 2011 to March 2021, 122 patients with resection and reconstruction involving pelvic area II were retrospectively analyzed. Among them, 17 had postoperative dislocation, 32 had pelvic area II, and 31 had pelvic area I+II. There were 40 cases in the pelvic area II+III, and 19 cases in the pelvic area I+II+III. There were 49 female patients and 73 male patients; the mean age was 47 years (9-73 years). The Musculoskeletal Tumor Society (MSTS) score of lower extremity patients after reduction was evaluated, and the clinical characteristics of dislocation, such as dislocation direction, dislocation time and reduction method, were counted and analyzed, and feasible prevention measures were analyzed based on the imaging characteristics after resection and reconstruction. dislocation method.Results:Among the 122 patients, there were 17 cases of dislocation, and the dislocation rate was 13.7%. Among them, 12 cases were anterior dislocation, accounting for 70.6% of anterior dislocation; 5 cases were posterior dislocation, and the proportion of posterior dislocation was 29.4%, difference (χ 2=4.52, P=0.033). There were 12 cases of dislocation within 3 months after operation, accounting for 70.6%; 1 case of dislocation occurred in 5 months after operation, and the other 4 cases of dislocation occurred for more than one year. The MSTS score of the dislocation patients after reduction was 56.1±15.6% (20%-80%). Combined with postoperative imaging examinations, the feasible methods for preventing dislocation include: The anteversion angle of the acetabular cup can be appropriately reduced (0°-10°); The acetabular cup can be appropriately shifted to the rear of the rotation center; Appropriately reducing the anteversion angle of the femoral neck prosthesis, the combination of the three can reduce the occurrence of femoral-acetabular prosthesis impingement; at the same time, the affected limb is controlled in a neutral position with strict nail shoes after surgery to avoid the occurrence of external rotation. Conclusion:The dislocation after tumor resection and reconstruction in pelvic area II is mostly anterior dislocation. Postoperative CT scan of the pelvis shows that the space between the neck of the femoral stem prosthesis and the lower edge of the acetabulum is small, which is prone to impingement. If the anteversion angle of the acetabular cup is appropriately reduced, the acetabular prosthesis is appropriately displaced posteriorly, and the anteversion angle of the femoral neck is reduced by 5°, the possibility of femoral-acetabular impingement can be reduced, thereby reducing the risk of postoperative dislocation.
10.Risk factors and functional evaluation of recurrence after resection of thigh soft tissue malignant tumor
Hao QU ; Keyi WANG ; Wei SHI ; Haochen MOU ; Jiadan WU ; Junyan XIE ; Cong WANG ; Hengyuan LI ; Xiumao LI ; Peng LIN ; Xiaobo YAN ; Meng LIU ; Xin HUANG ; Cong LIN ; Zhaoming YE
Chinese Journal of Orthopaedics 2023;43(12):841-848
Objective:To explore the risk factors of recurrence after resection of thigh soft tissue malignant tumors and the evaluation of the postoperative lower limb function.Methods:A total of 211 patients who underwent thigh soft tissue malignant tumor resection in the Department of Orthopaedics of the second affiliated Hospital of Medical College of Zhejiang University from May 2011 to May 2021 were retrospectively analyzed, including 117 males and 94 females, aged 53 (43, 65) years. There were 59 cases of atypical/well-differentiated liposarcoma, 30 cases of other types of liposarcoma, 33 cases of malignant fibrous histiocytoma, 19 cases of fibrosarcoma, 12 cases of rhabdomyosarcoma, 12 cases of leiomyosarcoma, 9 cases of synovial sarcoma, and 37 cases of others. The tumor involvement of muscle, bone, blood vessel, nerve tissue and intermuscular compartment, postoperative Musculoskeletal Tumor Society (MSTS) functional score and recurrence were recorded. The relationship between anatomical structure and postoperative recurrence was analyzed by Cox logistic regression to determine risk factors; the cumulative recurrence rate of different compartment groups (medial compartment, anterior compartment, and posterior compartment) were compared; The Box plot was used to compare the postoperative function of patients with resection of different anatomical structures (e.g., vastus lateralis, biceps femoris, femur, etc.).Results:A total of 34 out of 211 patients relapsed, with a recurrence rate of 16.1%. The recurrence time ranged from 2.6 months to 91.6 months after operation, with a median recurrence time of 37.0 (18.2, 52.8) months. Three independent risk factors were found to be associated with recurrence, namely: pathological grade [ HR=3.86, 95% CI(1.75, 8.51)], involvement of vastus intermedius [ HR=3.05, 95% CI(1.53, 6.06)], and involvement of vastus medialis [ HR=3.17, 95% CI(1.56, 6.41)]. The recurrence rate of patients with anterior chamber tumor resection was 35.3%, which was higher than that of patients without tumor resection (16.2%), and the difference was statistically significant ( P=0.020). There was no significant difference in recurrence rate between patients with medial chamber tumor resection and patients without tumor resection ( P>0.05). The recurrence rate of patients with posterior compartment tumor resection was 12.3%, which was lower than that of unresectable patients (37.6%), and the difference was statistically significant ( P=0.002).The postoperative MSTS score of 167 patients averaged 26±3.2 points (9-30 points). After intraoperative resection of part of the femur, vastus intermedius, vastus medialis, and rectus femoris, the patient's function was relatively poor [corresponding median MSTS score: 25 (23, 28), 26 (24 28), 26 (24,28), 26(24, 27)]. Conclusion:The risk factors for local recurrence after resection of thigh soft tissue malignant tumors include: pathological grade of the tumor, and whether the vastus intermedius or vastus medialis is involved. Anterior compartment tumors have a higher recurrence rate after surgery. If the tumor involves the above-mentioned anatomical structures, more attention should be paid to the risk of local recurrence after surgery.