Preparation and in vitro evaluation of fused deposition modeling 3D printed compound tablets of captopril and hydrochlorothiazide / 北京大学学报(医学版)

OBJECTIVE@#To explore the feasibility of preparing compound tablets for the treatment of hypertension by fused deposition modeling (FDM) 3D printing technology and to evaluate the quality of the printed compound tablets in vitro.@*METHODS@#Polyvinyl alcohol (PVA) filaments were used as the exci-pient to prepare the shell of tablet. The ellipse-shaped tablets (the length of major axes of ellipse was 20 mm, the length of the minor axes of ellipse was 10 mm, the height of tablet was 5 mm) with two separate compartments were designed and printed using FDM 3D printer. The height of layer was 0.2 mm, and the thickness of roof or floor was 0.6 mm. The thickness of shell was 1.2 mm, and the thickness of the partition wall between the two compartments was 0.6 mm. Two cardiovascular drugs, captopril (CTP) and hydrochlorothiazide (HCT), were selected as model drugs for the printed compound tablet and filled in the two compartments of the tablet, respectively. The microscopic morphology of the tablets was observed by scanning electron microscopy (SEM). The weight variation of the tablets was investigated by electronic scale. The hardness of the tablets was measured by a single-column mechanical test system. The contents of the drugs in the tablets were determined by high performance liquid chromatography (HPLC), and the dissolution apparatus was used to measure the in vitro drug release of the tablets.@*RESULTS@#The prepared FDM 3D printed compound tablets were all in good shape without printing defects. The average weight of the tablets was (644.3±6.55) mg. The content of CTP and HCT was separately (52.3±0.26) mg and (49.6±0.74) mg. A delayed in vitro release profile was observed for CTP and HCT, and the delayed release time for CTP and HCT in vitro was 20 min and 40 min, respectively. The time for 70% of CTP and HCT released was separately 30 min and 60 min.@*CONCLUSION@#CTP and HCT compound tablets were successfully prepared by FDM 3D printing technology, and the printed tablets were of good qualities.

Anterior Cingulate Cortex Mediates Hyperalgesia and Anxiety Induced by Chronic Pancreatitis in Rats / 神经科学通报·英文版

Central sensitization is essential in maintaining chronic pain induced by chronic pancreatitis (CP), but cortical modulation of painful CP remains elusive. Here, we examined the role of the anterior cingulate cortex (ACC) in the pathogenesis of abdominal hyperalgesia in a rat model of CP induced by intraductal administration of trinitrobenzene sulfonic acid (TNBS). TNBS treatment resulted in long-term abdominal hyperalgesia and anxiety in rats. Morphological data indicated that painful CP induced a significant increase in FOS-expressing neurons in the nucleus tractus solitarii (NTS) and ACC, and some FOS-expressing neurons in the NTS projected to the ACC. In addition, a larger portion of ascending fibers from the NTS innervated pyramidal neurons, the neural subpopulation primarily expressing FOS under the condition of painful CP, rather than GABAergic neurons within the ACC. CP rats showed increased expression of vesicular glutamate transporter 1, and increased membrane trafficking and phosphorylation of the N-methyl-D-aspartate receptor (NMDAR) subunit NR2B and the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) subunit GluR1 within the ACC. Microinjection of NMDAR and AMPAR antagonists into the ACC to block excitatory synaptic transmission significantly attenuated abdominal hyperalgesia in CP rats, which was similar to the analgesic effect of endomorphins injected into the ACC. Specifically inhibiting the excitability of ACC pyramidal cells via chemogenetics reduced both hyperalgesia and comorbid anxiety, whereas activating these neurons via optogenetics failed to aggravate hyperalgesia and anxiety in CP rats. Taken together, these findings provide neurocircuit, biochemical, and behavioral evidence for involvement of the ACC in hyperalgesia and anxiety in CP rats, as well as novel insights into the cortical modulation of painful CP, and highlights the ACC as a potential target for neuromodulatory interventions in the treatment of painful CP.

Difficult and complicated oral ulceration: an expert consensus guideline for diagnosis / 国际口腔科学杂志·英文版

The complexity of oral ulcerations poses considerable diagnostic and therapeutic challenges to oral specialists. The expert consensus was conducted to summarize the diagnostic work-up for difficult and complicated oral ulcers, based on factors such as detailed clinical medical history inquiry, histopathological examination, and ulceration-related systemic diseases screening. Not only it can provide a standardized procedure of oral ulceration, but also it can improve the diagnostic efficiency, in order to avoid misdiagnosis and missed diagnosis.

Cross-talk between CXC chemokine ligand 10-CXC chemokine receptor 3 axis and CC chemokine ligand 17-CC chemokine receptor 4 axis in the pathogenesis of oral lichen planus / 华西口腔医学杂志

OBJECTIVES@#This study aimed to determine whether a correlation existed between CXC chemokine ligand 10 (CXCL10)-CXC chemokine receptor 3 (CXCR3) and CC chemokine ligand 17 (CCL17)-CC chemokine receptor 4 (CCR4) in the pathogenesis of oral lichen planus (OLP).@*METHODS@#Peripheral blood of OLP patients (non-erosive and erosive groups) and healthy controls were collected, and T cells were isolated and purified. T cells were co-cultured with three groups: blank, anti-CXCR3, and anti-CCR4. CXCR3 and CCR4 expression were detected by flow cytometry, and CXCL10 and CCL17 were detected by enzyme-linked immunosorbent assay, respectively.@*RESULTS@#The purities of T cells were all >95% in the three groups (@*CONCLUSIONS@#Two axes interact with each other in the pathogenesis of OLP and may play different roles in its occurrence and development.

Analysis on Role of mTORC1/4E-BP1 Axis in Idiopathic Pulmonary Fibrosis and Research Progress of Bupleuri Radix on Its Intervention / 中国实验方剂学杂志

Idiopathic pulmonary fibrosis （IPF） is a common， lethal interstitial lung disease characterized by airway remodeling， inflammation， alveolar destruction， and fibrosis. The mammalian target of rapamycin complex 1/4E binding protein 1 （mTORC1/4E-BP1） axis is closely related to the expression of collagen by fibroblasts， and its role in pulmonary fibrosis remains to be further elucidated. Traditional Chinese medicine （TCM） has shown promising efficacy in improving the lung function， exercise capacity， and quality of life in patients with IPF. The theory of "same treatment for different diseases" provides a TCM theoretical basis for the treatment of pulmonary fibrosis with Bupleuri Radix， while the research in western medicine has preliminarily shown that both the formulation and single herb as well as the active ingredients of Bupleuri Radix have good therapeutic effects on pulmonary fibrosis. Therefore， this review will elaborate on the role of the mTORC1/4E-BP1 axis in the pathomechanism of IPF， as well as the research results of the active components of Bupleuri Radix on the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin protein（PI3K/AKT/mTOR） pathway， so as to provide a reference for the treatment and drug development of IPF.

Preparation and in vitro evaluation of fused deposition modeling 3D printed verapa-mil hydrochloride gastric floating formulations / 北京大学学报(医学版)

OBJECTIVE@#To explore the feasibility of preparing gastric floating formulations by fused de-position modeling (FDM) 3D printing technology, to evaluate the in vitro properties of the prepared FDM 3D printed gastric floating formulations, and to compare the influence of different external shapes of the formulation with their in vitro properties.@*METHODS@#Verapamil hydrochloride and polyvinyl alcohol (PVA) were used as the model drug and the excipient, respectively. The capsule-shaped and hemisphere-shaped gastric floating formulations were then prepared by FDM 3D printing. The infill percentages were 15%, the layer heights were 0.2 mm, and the roof or floor thicknesses were 0.8 mm for both the 3D printed formulations, while the number of shells was 3 and 4 for capsule-shaped and hemisphere-shaped formulation, respectively. Scanning electron microscopy (SEM) was used to observe the morpho-logy of the surface and cross section of the formulations. Gravimetric method was adopted to measure the weights of the formulations. Texture analyzer was employed to evaluate the hardness of the formulations. High performance liquid chromatography method was used to determine the drug contents of the formulations. The in vitro floating and drug release behavior of the formulations were also characterized.@*RESULTS@#SEM showed that the appearance of the FDM 3D printed gastric floating formulations were both intact and free from defects with the filling structure which was consistent with the design. The weight variations of the two formulations were relatively low, indicating a high reproducibility of the 3D printing fabrication. Above 800.0 N of hardness was obtained in two mutually perpendicular directions for the two formulations. The drug contents of the two formulations approached to 100%, showing no drug loss during the 3D printing process. The two formulations floated in vitro without any lag time, and the in vitro floating time of the capsule-shaped and hemisphere-shaped formulation were (3.97±0.41) h and (4.48±0.21) h, respectively. The in vitro release of the two formulations was significantly slower than that of the commercially available immediate-release tablets.@*CONCLUSION@#The capsule-shaped and hemisphere-shaped verapamil hydrochloride gastric floating formulations were prepared by FDM 3D printing technology successfully. Only the floating time was found to be influenced by the external shape of the 3D printed formulations in this study.

Diagnostic Performance of ⁶⁸Gallium Labelled Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography and Magnetic Resonance Imaging for Staging the Prostate Cancer with Intermediate or High Risk Prior to Radical Prostatectomy: A Systematic Review and Meta-analysis

PURPOSE: To compare the diagnostic efficiency of ⁶⁸Gallium labelled prostate-specific membrane antigen positron emission tomography (⁶⁸Ga-PSMA PET) and magnetic resonance imaging (MRI) for staging the lymph node metastases (LNMs) in the prostate cancer.MATERIALS AND METHODS: A broad search of scientific databases including PubMed, EMBASE, Web of Science, Cochrane Database, and Chinese Biomedicine Literature Database (updated prior to November 1st, 2018) was conducted systematically by two reviewers. In this paper, we evaluated the methodological quality of each included article independently and performed a systematic review and meta-analysis to reveal the summary of the diagnostic performance of ⁶⁸Ga-PSMA PET and MRI in properly identifying LNMs of intermediate- and/or high-risk prostate cancer.RESULTS: Thirteen eligible articles comprising 1,597 patients were included. For LNMs detection, the pooled sensitivity and specificity of ⁶⁸Ga-PSMA PET were 0.65 (95% confidence interval [CI]: 0.49–0.79) and 0.94 (95% CI: 0.88–0.97), respectively, while the corresponding values of MRI were 0.41 (95% CI: 0.26–0.57) and 0.92 (95% CI: 0.86–0.95). The area under the symmetric receiver-operating characteristic (SROC) curve for ⁶⁸Ga-PSMA PET and MRI were 0.92 and 0.83, respectively.CONCLUSIONS: In intermediate- or high-risk pre-treatment prostate cancer, ⁶⁸Ga-PSMA PET had a higher sensitivity and a slightly different specificity in probing the LNMs when comparing with MRI. Moreover, the area under the SROC curve indicated that ⁶⁸Ga-PSMA PET was a more effective weapon for predicting the LNMs prior to radical surgery.

Advances in the pathogenesis, diagnosis and treatment of thyroid follicular carcinoma / 医学研究生学报

Thyroid follicular carcinoma (FTC) is one of the highly differentiated malignant tumors second only to papillary thyroid carcinoma (PTC). Its occurrence is mainly caused by the abnormal differentiation of thyroid follicular epithelial cells. Lymph node metastasis around FTC is rare, but distant tissue metastasis is more common. At present, there are few studies on the pathogenesis of FTC. The clinical diagnosis and treatment of FTC are mainly focused on imaging examination, fine needle aspiration and so on. Surgical resection is the main clinical treatment, with unfavourable prognosis. In this paper, the epidemiology, pathogenesis, diagnosis and treatment of FTC were summarized, and the research progress of FTC was reviewed.

Research advances in the association between NF-κB signaling pathway and hepatitis C virus infection / 医学研究生学报

The nuclear factor-κB (NF-κB) pathway plays an important role in cell proliferation, survival, early viral response, cytokine secretion, and pro-inflammatory. Hepatitis C virus (HCV) can hijack and interact with the NF-κB signaling pathway and affect disease outcomes. This paper describes the interaction between NF-κB protein family, signaling pathway, HCV viral protein and host NF-κB signaling pathway, and its effect on HCV infection. In the future, further study is expected to be done in this aspect to provide new strategies for the screening of HCV high-susceptibility population as well as prevention.

Ethical thinking and effect research of multiple comprehensive psychological intervention measures used in intensive care unit / 中国中西医结合急救杂志

Objective To discuss the ethical necessity and feasibility of implementing multiple comprehensive psychological intervention measures in intensive care unit (ICU), and to investigate the effect of the measures on treatment compliance. Methods The conscious adult patients hospitalized in emergency ICU (EICU) of the Second Affiliated Hospital of Xi'an Jiaotong University from 2015 to 2017 were enrolled, and divided into control group and intervention group according to random number table, with 40 patients in each group. Patients in control group were treated with routine care and routine diagnosis and treatment, and patients in intervention group were treated with the help of psychologists and with multiple comprehensive psychological intervention measures (including nursing care, medical treatment, family and management) based on routine care and routine diagnosis and treatment. After 5 days of intervention, the treatment compliance, the medical coping attitude and the mental health were assessed respectively using the Treatment Compliance Scale, the Medical Coping Modes Questionnaire (MCMQ) and the Symptom Checklist Scale (SCL-90), and then comparation were done between the two groups. Results After 5 days of intervention, 3 patients in the control group and 4 patients in the intervention group withdraw the study because of the change of illness, and at last 37 patients in the control group and 36 in the intervention group were enrolled. There was no significant difference in basic data such as gender, age, education level, disease, course of disease, the length of EICU stay, and acute physiology and chronic health evaluationⅡ (APACHEⅡ) score between the two groups. The scores of treatment compliance in intervention group was significantly higher than that in control group (2.89±0.67 vs. 2.32±0.91, P < 0.01). Compared with the control group, the "confrontation" dimension score of the MCMQ questionnaire in intervention group was significantly increased (19.75±2.08 vs. 18.62±2.65, P < 0.05), while the "avoidance" and"surrender" dimensions scores were significantly decreased (14.22±1.91 vs. 15.14±1.92, 8.83±1.54 vs. 9.73±2.10, both P < 0.05). In the SCL-90 scale, the scores of the 5 factors such as "somatization", "interpersonal sensitivity","depression", "anxiety" and "photic anxiety" in intervention group were significantly less than those in control group (1.59±0.38 vs. 1.81±0.37, 1.72±0.40 vs. 1.93±0.42, 1.76±0.32 vs. 1.92±0.29, 1.82±0.40 vs. 2.14±0.40, 1.44±0.30 vs. 1.60±0.38, all P < 0.05), while there was no significantly difference in the scores of the other 4 factors as "obsessive-compulsive symptoms", "hostile", "bigotry" and "psychoticism" between the two groups (all P > 0.05). Conclusion The multiple comprehensive psychological intervention measures used for ICU conscious patients could improve the treatment compliance, make the patients' medical coping attitude more active and improve the mental health of the patients, so it has ethical necessity and certain feasibility.

Effects of CeA lesions on the initiation and expression of sodium appetite in sodium-deficient rats / 中国应用生理学杂志

OBJECTIVE@#To investigate the effects of central nucleus of amygdala (CeA) lesion on the initiation and expression of sodium appetite in sodium-deficient rats.@*METHODS@#Three groups of SD rats (n=6 in each group) were treated with bilateral CeA lesion, sham lesion or no lesion. After the recovery, the rats were fed with low-sodium diets for 14 days to establish a sodium-deficient rat model. The double-bottle selection in single cage test was used to observe the intake of 0.3 mol/L NaCl and DW in 5 timepoint with 24 hours in sodium-deficient rats. Immunofluorescence staining of aldosterone-sensitive neurons in the nucleus tractus solitarii (NTS)was used to investigate the effect of CeA lesion or not on the activity of aldosterone-sensitive neurons in rats with or without sodium deficiency.@*RESULTS@#After fed with low-sodium diet for14 days, the volume and preference rate of 0.3 mol/L NaCl intake of the rats within 24 h were significantly increased compared with those before low-sodium diet (P＜0.01). The intake volume and the preference rate of 0.3 mol/L NaCl in CeA lesion rats were significantly decreased than those in CeA sham lesion rats and normal rats in the sodium-deficient condition (P＜0.01). The CeA lesion had no effects on the activity of aldosterone-sensitive neurons in NTS in rats with low-sodium diet.@*CONCLUSION@#Low-sodium diet induces an increase in the expression of sodium appetite in rats. CeA lesions inhibit the behavioral expression of sodium appetite in sodium-deficient rats but have no effects on the initiation of sodium appetite in rats with sodium-deficient rats.

Value of intra-operative Doppler sonographic measurements in predicting post-operative anastomotic leakage in rectal cancer: a prospective pilot study / 中华医学杂志(英文版)

Background@#Anastomotic leakage is a serious surgical complication in rectal cancer; however, effective evaluation methods for predicting anastomotic leakage individual risk in patients are not currently available. This study aimed to develop a method to evaluate the risk of leakage during surgery.@*Methods@#The 163 patients with rectal cancer, who had undergone anterior resection and low-ligation procedures for Doppler sonographic hemodynamic measurement from April 2011 to January 2015 in Peking University Cancer Hospital, were prospectively recruited. A predictive model was constructed based on the associations between anastomotic leakage and alterations in the anastomotic blood supply in the patients, using both univariate and multivariate statistical analyses, as well as diagnostic methodology evaluation, including Chi-square test, logistic regression model, and receiver operating characteristic curve.@*Results@#The overall anastomotic leakage incidence was 9.2% (15/163). Doppler hemodynamic parameters whose reduction was significantly associated with anastomotic leakage were peak systolic velocity, pulsatility index, and resistance index. The areas under the receiver operating characteristic curve of residual rates of peak systolic velocity, pulsatility index, and resistance index in predicting anastomotic leakage were 0.703 (95% confidence interval [CI]: 0.552–0.854), 0.729 (95% CI: 0.579–0.879), and 0.689 (95% CI: 0.522–0.856), respectively. The predictive model revealed that the patients with severely reduced blood-flow signal exhibited a significantly higher incidence rate of anastomotic leakage than those with sufficient blood supply (19.6% vs. 3.7%, P = 0.003), particularly the patients with low rectal cancer (25.9% vs. 3.9%, P = 0.007) and those receiving neoadjuvant chemoradiotherapy (32.1% vs. 3.7%, P = 0.001), independent of prophylactic ileostoma. Multivariate analysis revealed that insufficient blood supply of the anastomotic bowel was an independent risk factor for anastomotic leakage (odds ratio: 10.37, 95% CI: 2.703–42.735, P = 0.001).@*Conclusion@#Based on this explorative study, Doppler sonographic hemodynamic measurement of the anastomotic bowel presented potential value in predicting anastomotic leakage.

Value of intra-operative Doppler sonographic measurements in predicting post-operative anastomotic leakage in rectal cancer: a prospective pilot study / 中华医学杂志(英文版)

BACKGROUND@#Anastomotic leakage is a serious surgical complication in rectal cancer; however, effective evaluation methods for predicting anastomotic leakage individual risk in patients are not currently available. This study aimed to develop a method to evaluate the risk of leakage during surgery.@*METHODS@#The 163 patients with rectal cancer, who had undergone anterior resection and low-ligation procedures for Doppler sonographic hemodynamic measurement from April 2011 to January 2015 in Peking University Cancer Hospital, were prospectively recruited. A predictive model was constructed based on the associations between anastomotic leakage and alterations in the anastomotic blood supply in the patients, using both univariate and multivariate statistical analyses, as well as diagnostic methodology evaluation, including Chi-square test, logistic regression model, and receiver operating characteristic curve.@*RESULTS@#The overall anastomotic leakage incidence was 9.2% (15/163). Doppler hemodynamic parameters whose reduction was significantly associated with anastomotic leakage were peak systolic velocity, pulsatility index, and resistance index. The areas under the receiver operating characteristic curve of residual rates of peak systolic velocity, pulsatility index, and resistance index in predicting anastomotic leakage were 0.703 (95% confidence interval [CI]: 0.552-0.854), 0.729 (95% CI: 0.579-0.879), and 0.689 (95% CI: 0.522-0.856), respectively. The predictive model revealed that the patients with severely reduced blood-flow signal exhibited a significantly higher incidence rate of anastomotic leakage than those with sufficient blood supply (19.6% vs. 3.7%, P = 0.003), particularly the patients with low rectal cancer (25.9% vs. 3.9%, P = 0.007) and those receiving neoadjuvant chemoradiotherapy (32.1% vs. 3.7%, P = 0.001), independent of prophylactic ileostoma. Multivariate analysis revealed that insufficient blood supply of the anastomotic bowel was an independent risk factor for anastomotic leakage (odds ratio: 10.37, 95% CI: 2.703-42.735, P = 0.001).@*CONCLUSION@#Based on this explorative study, Doppler sonographic hemodynamic measurement of the anastomotic bowel presented potential value in predicting anastomotic leakage.

The application of HC visual laryngoscope used for emergency tracheal intubation on obese patients in Emergency Department / 中华急诊医学杂志

Objective To investigate the effect and application value of HC visual laryngoscope used for the emergency tracheal intubation on obese patients in the Emergency Department. Methods Totally 80 obese patients enrolled from January 2014 to December 2016 from Emergency Department, Second affiliated hospital of Xi'an Jiaotong University who needed the emergency tracheal intubation were randomly (random number) divided into two groups. Patients in group T were operated with traditional laryngoscope, and patients in group HC with HC visual laryngoscope. Then the success rate of glottis exposure, the trial times, operative time, success rate and complication rate of tracheal intubation were compared between the two groups. Results The success rate of glottis exposure in group HC was significantly higher than that in group T (95％ vs 77.5％, P<0.05). The one-time success rate of tracheal intubation and the total success rate of tracheal intubation in group HC were significantly higher than those in group T (72.5％ vs 37.5％, and 95％ vs 62.5％, respectively, P<0.05). However, the trial times of successful intubation cases and the operative time of successful intubation cases were significantly less than those in group T (1.26±0.40) vs (1.64±0.82), and (30.74±6.17) s vs (44.2±7.68) s, respectively, P<0.05. The complication rate of tracheal intubation in group HC was significantly less than that in group T (12.5％ vs 35％, P<0.05). Conclusions HC visual laryngoscope used for the obese patients in Emergency Department can not only increase the success rate of glottis exposure, decrease trial times and shorten operative time of intubation, but also improve the success rate and decrease the complication rate of emergency tracheal intubation, thus having a certain application value.

Inhibition of High Glucose-induced Apoptosis of Pancreatic β-cells by Gallic Acid in Phyllanthus Emblica / 昆明医科大学学报

Objective To explore the protective effect of gallic acid in Phyllanthus emblica on high glucose－induced apoptosis of pancreatic islet β cells, and to provide a reference for the discovery of natural compounds for the treatment of diabetes. Methods In vivo experimental model, wistar male rats were used as in vivo subjects and 50 mg/kg STZ was injected intraperitoneally. After the model was successfully established, 25 mg/kg of gallic acid was given orally, and the positive drug was Sitagliptin. After 4 weeks of administration, the blood was taken and the pancreas was removed for HE staining. Western blot was used to measure the expression of NLRP3 and TXNIP in pancreatic tissue in high sugar state. In vitro model, insulinoma cell line INS－1 cells were used as in vitro targets to establish high levels. In sugar－induced apoptosis model, INS－1 cells were cultured in glucose－free RPMI 1640 complete medium supplemented with 25 mmol/L glucose. Gallic acid was used as the test sample. Experiments were divided into normal controls, high－sugar models, and low, medium and high levels of gallic acid groups. The cell viability was measured by MTT assay. The mRNA expression of NLRP3 and TXNIP in INS－1 cells was detected by QPCR and Western blot, and the expression of NLRP3 and TXNIP protein was detected.Results (1) INS－1 cells were cultured in a medium with glucose concentration of 25mmol/L for 48h, and the apoptosis rate was increased compared with the control group (P＜0.01), indicating that the apoptosis model was established successfully under high glucose conditions. (2) 10, 5, and 2.5 μmol/L GA were used to treat the control group and the high glucose model group cells respectively. The survival rate of the control group did not change significantly (P＞0.05) . Compared with the control group, the expression of NLRP3 and TXNIP in INS－1 cells in the high glucose model group was significantly different (P＜0.05);the protein expression level was significantly downregulated after GA treatment, and there was a statistical difference (P＜0.05) . Compared with the control group, the expression of NLRP3 protein in INS－1 cells in the high glucose model group was statistically different (P＜0.01), and the protein expression level was significantly downregulated after GA treatment (P＜0.01) ; The protein expression level was up－regulated (P＜0.05);the protein expression level after GA treatment was significantly down－regulated (P＜0.05); (4) The expression of NLRP3 and TXNIP mRNA in INS－1 cells was increased in the high glucose model group compared with the control group (P＜0.01) ; The expression of protein was significantly down－regulated after GA treatment (P＜0.01) . Conclusion The cells were cultured for 48 h in glucose－free RPMI 1640 complete medium supplemented with 25 mmol/L glucose. GA has no effect on the proliferation of normal INS－1 cells. GA protects INS－1 cells from apoptosis under high glucose conditions. The mechanism may be related to GA down－regulation of NLRP3 and TXNIP gene expression.

Thyroid Papillary Carcinoma Cells TPC-1 Apoptosis Induced by Ursolic Acid / 昆明医科大学学报

Objective To study the inhibitory effect of ursolic acid on the proliferation of human papillary thyroid carcinoma cell line TPC-1 in vitro. Method TPC-1 cells were treated with different concentrations of ursolic acid (control group:0μM, experimental group:3μM , 6μM, 12μM);MTT assay was used to observe the effect of the growth of TPC-1 cells on different concentrations of ursolic acid at the same time;Apoptosis and cell cycle distribution of TPC-1 cells were treated with ursolic acid by flow cytometry;The expression of Bcl-2, Bax and Caspase-9 mRNA in TPC-1 cells were treated with ursolic acid by QRT-PCR;The expression of Bcl-2, Bax and Caspase-9 protein in TPC-1 cells were treated with ursolic acid by Western blot. Results MTT assay showed that ursolic acid inhibited the proliferation of TPC-1 cells in a concentration and time-dependent manner, and the IC50 at 24 h, 48 h and 72 h was 14.21 μM, 10.56 μM, 10.39 μM; Flow cytometry showed that ursolic acid inhibited the apoptosis of TPC-1 cells in a concentration-dependent manner, and the growth of TPC-1 cells was arrested in S phase;QRT-PCR showed that Bcl-2, Bax and Caspase-9 mRNA were expressed in the control and experimental groups, ursolic acid inhibited the expression of Bcl-2 mRNA in a concentration-dependent manner and up-regulated the expression of Bax and Caspase-9 mRNA;Western blot results showed that Bcl-2, Bax and Caspase-9 were expressed in the control and experimental groups, ursolic acid inhibited the expression of Bcl-2 protein in a concentration-dependent manner and up-regulated the expression of Bax protein and Caspase-9 protein. Conclusion Ursolic acid can significantly inhibit the proliferation and induce apoptosis of human papillary thyroid TPC-1 cells, providing some ideas for the treatment of thyroid cancer.

Preparation and characterization of citric acid-modified superparamagnetic iron oxide nanoparticles / 北京大学学报(医学版)

OBJECTIVE@#To prepare and characterize citric acid (CA)-modified super paramagnetic iron oxide nanoparticles (SPIONs) for magnetic targeting, hyperthermia and magnetic resonance imaging (MRI).@*METHODS@#CA-modified SPIONs (CA-SPIONs) were prepared by co-precipitation method and then the magnetic responsiveness, morphology, particle size, infrared feature, weight percentage of CA, magnetic property and X-ray diffraction pattern of CA-SPIONs were respectively characterized by magnet, transmission electron microscope, laser particle size analyzer, Fourier transform infrared (FT-IR) spectroscopy, thermogravimetry-differential thermal analyzer, vibrating sample magnetometer and X-ray diffractometer (XRD). The heating efficiency of the CA-SPIONs was investigated by a high frequency induction heater. The transverse relaxivity (r2) of the CA-SPIONs was evaluated by a 3.0 T MRI scanner.@*RESULTS@#The CA-SPIONs prepared were dispersed well in water with a dark black color and had good magnetic responsiveness. The CA-SPIONs were spherical in shape and uniform in size with an average size around 12 nm. The hydrodynamic average size of the CA-SPIONs was (72.35±4.47) nm with a polydispersity index of 0.231 ± 0.029. The result of infrared spectrum indicated that CA was successfully modified to the surface of SPIONs. The result of thermogravimetric analysis showed that the weight percentage of CA modified on the CA-SPIONs was 9.0%. The result of magnetic property evaluation demonstrated that the CA-SPIONs exhibited excellent superparamagetism with a saturation magnetism of 63.58 emu/g. The XRD result indicated that the CA-SPIONs were in inverse spinel structure. The crystallite size of the CA-SPIONs was calculated to be 12.4 nm by Debye-Scherrer equation. Under the high frequency alternating electromagnetic field with electric current of 9 A and frequency ranging from 45 to 50 kHz, the CA-SPIONs exhibited excellent heating efficiency and the specific absorption rate (SAR) value was calculated to be 26 W/g. The r2 of the CA-SPIONs was assessed to be 338 (mmol/L)-1×s-1 by a 3.0 T MRI scanner, which suggested the excellent negative contrast enhancement effect of the CA-SPIONs.@*CONCLUSION@#The CA-SPIONs are expected to be used as a promising agent for magnetic targeting, hyperthermia and MRI detection.

Preparation and evaluation of blank and doxorubicin loaded poly (acrylic acid) microspheres for embolization / 北京大学学报(医学版)

OBJECTIVE@#To prepare ion exchange doxorubicin-loaded poly (acrylic acid) microspheres (DPMs) and evaluate the properties of these chemoembolic agents.@*METHODS@#Poly (acrylic acid) microspheres (PMs) without drug were prepared by inverse suspension polymerization method and then doxorubicin was loaded by ion exchange mechanism to prepare DPMs. Optical microscope was used to investigate the morphology and particle size distribution of PMs and DPMs; fluorescence microscope and confocal microscope were used to observe the distribution of doxorubicin after drug loading. Elasticities of both the microspheres were evaluated by texture analyzer. High performance liquid chromatography (HPLC) method was established to determine the drug loading behavior of PMs and releasing behavior of DPMs. The in vivo embolic property was evaluated by embolizing the hepatic artery of a rabbit with 0.1 mL of DPMs.@*RESULTS@#PMs and DPMs were both spherical in shape, smooth in surface and dispersed well. Doxorubicin was mainly in the outer area inside of DPMs and distributed evenly. The average particle size of PMs and DPMs were (283±136) μm and (248±149) μm, respectively. PMs and DPMs both had good compression ability with the Young's modulus of (62.63±1.65) kPa and (93.94±1.10) kPa separately. PMs reached the drug loading balance at 12 h, and the entrapment efficiency was greater than 99%. Drug loading of PMs in doxorubicin solution at the concentration of 5.0 g/L and 12.5 g/L was (19.78±0.27) g/L and (49.45±0.37) g/L, respectively. Doxorubicin released slowly from DPMs in PBS and the accumulative release percentages of DPMs with corresponding drug loading were 6.82%±0.02% and 2.83%±0.10% after 24 h, respectively. Arterial angiograms showed that the hepatic artery of the rabbit was successfully embolized with DPMs.@*CONCLUSION@#DPMs with good performance of loading doxorubicin could be a potential embolic agent for transcatheter arterial chemoembolization.

Content Determination of Gallic Acid, Corilagin and Ellagic Acid in Aqueous Extract from Sanguo Decoction by HPLC / 中国中医药信息杂志

Objective To establish an HPLC method for the simultaneous determination of contents of gallic acid, corilagin and ellagic acid in aqueous extract from Sanguo Decoction. Methods The analysis was carried out on an Agilent C18 column (4.6 mm × 250 mm, 5 μm), and the mobile phase was composed of acetonitrile and 0.1%phosphoric acid aqueous with gradient elution. The detection wavelength was 260 nm. The flow rate was 1.0 mL/min at column temperature of 30 ℃. Results Gallic acid, corilagin and ellagic acid were completely separated and the peak shape was good. It showed a good linearity in the concentration range of 0.174–2.61 μg, 0.04–0.60 μg, and 0.052–0.78 μg, respectively. The average recoveries of gallic acid, corilagin and ellagic acid were 99.98%, 99.81%and 100.12%, respectively. The RSD were less than 2.0%. Conclusion This method is rapid, accurate and repeatable, which can provide references for the quality control of Sanguo Decoction.

The effects and safety of triamcinolone acetonide oral ointment in the treatment of erosive oral lichen planus / 实用口腔医学杂志

Objective:To study the effects and safety of triamcinolone acetonide oral ointment in the treatment of erosive oral lichen planus(EOLP).Methods:62 cases with EOLP were randomly divided into 2 groups.The patients in test group(n =29) were treated by local application of triamcinolone acetonide oral ointment (TAOO),oral administration of hydmxychloroquine(HCQ) and gargle with cetylpyridinium chloride buccal tablets(CCBT),in control group (n =33) by HCQ and CCBT.The patients were followed up for 4 weeks.The changes of the erosion area and the VAS pain degree of the patients were analysed at the first visit,the second week and the fourth week follow-up respectively.The safety indexes were examined at the first visit and the fourth week follow-up respectively.Results:TAOO accelerated the erosion surface healing of EOLP in 2 weeks(P ＜ 0.05),and reduced the pain index of the patients (P＜0.05),but after 4 week treatment,no significant difference was observed between 2 groups (P ＞ 0.05).Fungal infection was found in 4 cases in test group.Conclusion:Local application of TAOO combined with oral administration of HCQ and gargle with CCBT is more effective than HCQ and CCBT in the treatment of EOLP,attention should be paid to prevent fungal infection.