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diagnosed with hepatic echinococcosis at three hospitals in western regions in China from 2014 to 2015.Venous blood was withdrawn to detect to liver function indications.ELISA was performed to detect HBsAg.We analyzed liver function in patients stratified by different types of hepatic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.

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.

Human with bi-allelic WNT10A mutations and epithelial Wnt10a knockout mice present enlarged pulp chamber and apical displacement of the root furcation of multi-rooted teeth,known as taurodontism;thus,indicating the critical role of Wnt10a in tooth root morphogenesis.However,the endogenous mechanism by which epithelial Wnt10a regulates Hertwig's epithelial root sheath(HERS)cellular behaviors and contributes to root furcation patterning remains unclear.In this study,we found that HERS in the presumptive root furcating region failed to elongate at an appropriate horizontal level in K14-Cre;Wnt10afl/flmice from post-natal day 0.5(PN0.5)to PN4.5.EdU assays and immunofluorescent staining of cyclin D1 revealed significantly decreased proliferation activity of inner enamel epithelial(IEE)cells of HERS in K14-Cre;Wnt10afl/flmice at PN2.5 and PN3.5.Immunofluorescent staining of E-Cadherin and acetyl-α-Tubulin demonstrated that the IEE cells of HERS tended to divide perpendicularly to the horizontal plane,which impaired the horizontal extension of HERS in the presumptive root furcating region of K14-Cre;Wnt10afl/flmice.RNA-seq and immunofluorescence showed that the expressions of Jag1 and Notch2 were downregulated in IEE cells of HERS in K14-Cre;Wnt10afl/fl mice.Furthermore,after activation of Notch signaling in K14-Cre;Wnt10afl/flmolars by Notch2 adenovirus and kidney capsule grafts,the root furcation defect was partially rescued.Taken together,our study demonstrates that an epithelial Wnt10a-Notch signaling axis is crucial for modulating HERS cell proper proliferation and horizontal-oriented division during tooth root furcation morphogenesis.

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.

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.

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.

Alzheimer’s disease (AD) is a neurodegenerative disorder involving multiple pathological processes, clinically characterized by memory loss and cognitive impairment. The pathological processes of AD are complex, and the etiology remains unclear. Currently, there are various hypotheses including β-amyloid (Aβ) deposition, tau protein hyperphosphorylation, neuroinflammation, and synaptic loss, upon which researchers base their drug development efforts. Prior to 2021, drugs approved by the U.S. Food and Drug Administration (FDA) had targeted neurotransmitter modulation, but their efficacy was limited. In recent years, the approval of two anti-Aβ monoclonal antibody drugs has brought some clinical benefits to patients, yet they have not fully met clinical needs, which had highlighted the urgent necessity for exploration of new mechanisms and targets in AD drug development. Presently, research on novel mechanisms and targets for AD drug development focuses primarily on several directions: anti-Aβ drugs, anti-Tau protein drugs, anti-neuroinflammation immunotherapies, mitochondrial function-improving drugs, neurogenesis-promoting drugs, and synapse-protective drugs. This paper provides an overview of AD drugs entering clinical trials in the past decade in these directions, details some representative drugs, and concludes with prospects, integrating findings from our research group.

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.

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.

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.