Preparation and in vitro evaluation of polylactic acid nanoparticles containing arginine and glucose oxidase / 药学学报

Hydrogen peroxide (H2O2) and nitric oxide (NO) has a short half-life, low bioavailability, poor tumor targeting and systemic adverse reactions in the physiological environment. In this study, phacoemulsification and nano-precipitation were used to synthesize didecyl dimethyl ammonium bromide (DDAB)/polylactic acid nanoparticles (PLA), then L-arginine (L-Arg) and glucose oxidase (GOx)-loaded nanoparticles (GADP) were prepared, and the in vitro antitumor activity was investigated．The particle size, potential, embedding rate and the ability to produce H2O2/NO of the nanoparticles were investigated. Meanwhile, in vitro cell cytotoxicity against human hepatoma cells (HepG2) was evaluated．The results showed that the prepared L-Arg-DDAB/PLA (ADP) nanoparticles were spherical particles. And the particle size and zeta potential were (225.7 ± 6.33) nm and (+23.5 ± 0.12) mV, respectively. The adsorption rate of GOx was 87.23% ± 0.02%. The drug loading of L-Arg was 15.6% ± 0.22%. The pH value of glucose solution and the amount of H2O2 showed that GADP had good catalytic activity. In vitro cytotoxicity experiments showed that blank nanoparticles were nontoxic, while the drug-loaded nanoparticles presented enhanced antitumor effect on HepG2 cells. And can inhibit tumor cell migration. The low dose nano-scale NO delivery system GADP can effectively inhibit the migration of tumor cells and kill tumor cells, thus producing therapeutic benefits.

Expression levels of serum nitric oxide and nitric oxide synthase intheUy-ghur and Han nationality patients with anti-tuberculosis drug-induced liver injury in Xinjiang / 中国感染控制杂志

Objective To explore the expression levels of serum nitric oxide(NO)and nitric oxide synthase(NOS) between Han and Uyghur nationality patients with anti-tuberculosis drug-induced liver injury(ATDLI). Methods Patients with confirmed ATDLI in Chest Hospital of Xinjiang Uyghur Autonomous Region and First Affiliated Hos-pital of the Medical College of Shihezi University between January 2015 and May 2016 were chosen and divided into Han group and Uyghur group.By detecting the expression levels of NO and NOS in serum of ATDLI patients,ex-pression levels of serum NO and NOS in ATDLI patients of different gender,body mass index(BMI),and liver function injury were compared.Results 100 ATDLI patients in Han group and 135 in Uyghur group were recruited in study. Expression levels of NO and TNOS in Han group were(134.24±27.60)μmol/L and(33.01 ±4.23)U/mL respectively,in Uyghur groups were(97.10±17.41)μmol/L and(27.41 ±3.95)U/mL respectively,serum levels of NO,TNOS,iNOS,and eNOS in Han patients were all higher than Uyghur patients,difference was statistically significant(P<0.01). In Han ATDLI group,serum levels of NO and TNOS in male patients were both higher than female patients(P<0.05);in Uyghur ATDLI group,serum levels of NO,TNOS,and iNOS in male patients were all higher than female patients(P<0.01). The expression levels of serum NO,TNOS,and iNOS of Han group were all higher than the same gender in Uyghur group(P<0.001),difference in levels of NO and TNOS among different body mass index(BMI)groups in Han and Uyghur patients were both statistically significant(P<0.01). In both group,levels of NO and TNOS in obese patients were both higher than lean patients and normal weight patients(P<0.05). The correlation analysis showed that NO levels of Han and Uyghur groups were both positively correlated with BMI(r=0.444,0.677,respectively,P<0.01). There were significant differences in serum NO and NOS levels between Han and Uyghur patients with different degrees of liver injury(P<0.05);NO and NOS levels in both groups with mild liver injury were both lower than those with moderate and severe injury (P<0.001).Conclusion Serum NO and NOS levels between ATDLI Han group and Uyghur group are different,serum NO level is related to BMI,and it can increase with the degree of liver injury.

Toll-like Receptor 4 Signaling Pathway in the Protective Effect of Pioglitazone on Experimental Immunoglobulin A Nephropathy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>In vitro experiments have revealed that toll-like receptor 4 (TLR4) pathway is involved in the progression of immunoglobulin A nephropathy (IgAN) by induction of proinflammatory cytokines. Evidence showed that, in other disease models, peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists have been shown to exert anti-inflammatory effects through suppression of the expression and activity of TLR4. However, the interaction between PPAR-γ and TLR4 in IgAN has not been fully studied both in vitro and in vivo. In this study, we explored whether TLR4 pathway attributed to the progression of IgAN in experimental rats.</p><p><b>METHODS</b>Bovine gamma globulin was used to establish IgAN model. Fifty-four Lewis rats were randomly divided into six groups: ControlTAK242, IgANTAK242, toll-like receptor 4 inhibitor (TAK242) groups (rats were administrated with TLR4 inhibitor, TAK242) and ControlPio, IgANPio, Pio groups (rats were administrated with PPAR-γ agonist, pioglitazone). Urinary albumin-to-creatinine ratio (ACR), serum creatinine, and blood urea nitrogen were detected by automatic biochemical analyzer. Renal histopathological changes were observed after hematoxylin-eosin staining, and the IgA deposition in glomeruli was measured by immunofluorescence staining. Real-time polymerase chain reaction and Western blotting were used to detect TLR4 and interleukin-1 beta (IL-1β) message ribonucleic acid (mRNA) and protein expression in renal tissues. Results were presented as mean ± standard deviation. Differences between groups were analyzed by one-way analysis of variance.</p><p><b>RESULTS</b>Compared to normal rats, experimental rats showed higher ACR (4.45 ± 1.33 mg/mmol vs. 2.89 ± 0.96 mg/mmol, P < 0.05), obvious IgA deposition with mesangial hypercellularity, hyperplasia of mesangial matrix accompanied by increased serum IL-1β (48.28 ± 13.49 pg/ml vs. 35.56 ± 7.41pg/ml, P < 0.05), and renal expression of IL-1β and TLR4. The biochemical parameters and renal pathological injury were relieved in both TAK242 group and Pio group. The expressions of renal tissue TLR4, IL-1β, and serum IL-1β were decreased in rats treated with TAK242, and the expression of TLR4 mRNA and protein was significantly reduced in Pio group compared to IgANPiogroup (1.22 ± 0.28 vs. 1.72 ± 0.45, P < 0.01, and 0.12 ± 0.03 vs. 0.21 ± 0.05, P < 0.01).</p><p><b>CONCLUSIONS</b>Our study proves that inflammation mediated by TLR4 signaling pathway is involved in the progression of IgAN in rat models. Moreover, pioglitazone can inhibit the expression of TLR4 in IgAN.</p>

Multi-parameter arterial spin labeling versus dynamic magnetic-sensitive enhanced cerebral perfusion imaging for diagnosis of transient cerebral ischemic attack / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the clinical value of three-dimensional pseudo-continuous arterial spin labeling (3D pCASL) perfusion magnetic resonance imaging (MRI) and dynamic susceptibility contrast (DSC) enhanced perfusion MRI in the diagnosis of transient ischemic attack (TIA).</p><p><b>METHODS</b>Thirty-nine consecutive patients with suspected TIA underwent multi-modal MRI scans including DSC, magnetic resonance angiography (MRA), diffusion-weighted imaging (DWI) and 3D pCASL (post-labeling delay, PLD=1.5 s and 2.5 s) within 24 h of symptom onset. Cerebral blood flow (CBF) from ASL and the time to the maximum of tissue residual function (Tmax) map from DSC were calculated using AW workstation. DWI and MRA were applied to detect acute cerebral infarction and intracranial artery stenosis. Two neuroradilogists who were blinded to the patients' clinical data assessed the presence of perfusion deficit, ischemic lesion and the lesion sites both from 1.5 s, 2.5 s PLD ASL-CBF and DSC-Tmax independently, and then graded them. The differences in the ranking grades between 1.5 s, 2.5 s PLD ASL and DSC were analyzed, and the frequency of lesion detection was compared between ASL-CBF, Tmax and MRA combining DWI method.</p><p><b>RESULTS</b>No significant differences was found in hypoperfusion grades detected by 3D pCASL (including PLD1.5 s and 2.5 s) CBF and Tmax maps, while significant differences were detected between 1.5 s PLD ASL-CBF and MRA combining DWI method; ASL with PLD 1.5 s CBF detected ischemic lesions and lesion site significantly more frequently than MRA combining DWI method.</p><p><b>CONCLUSION</b>s Three dimensional pCASL is a non-invasive perfusion method free of radiation exposure, and short PLD ASL is more sensitive than long PLD ASL for detecting ischemic lesions and lesion sites.</p>

Detection of Echinoderm Microtubule Associated Protein Like 4-Anaplastic Lymphoma Kinase Fusion Genes in Non-small Cell Lung Cancer Clinical Samples by a Real-time Quantitative Reverse Transcription Polymerase Chain Reaction Method / 中国医学科学院学报

Objective To establish a real-time quantitative reverse transcription polymerase chain reaction assay (qRT-PCR) for the rapid, sensitive, and specific detection of echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) fusion genes in non-small cell lung cancer. Methods The specific primers for the four variants of EML4-ALK fusion genes (V1, V2, V3a, and V3b) and Taqman fluorescence probes for the detection of the target sequences were carefully designed by the Primer Premier 5.0 software. Then, using pseudovirus containing EML4-ALK fusion genes variants (V1, V2, V3a, and V3b) as the study objects, we further analyzed the lower limit, sensitivity, and specificity of this method. Finally, 50 clinical samples, including 3 ALK-fluorescence in situ hybridization (FISH) positive specimens, were collected and used to detect EML4-ALK fusion genes using this method. Results The lower limit of this method for the detection of EML4-ALK fusion genes was 10 copies/μl if no interference of background RNA existed. Regarding the method's sensitivity, the detection resolution was as high as 1% and 0.5% in the background of 500 and 5000 copies/μl wild-type ALK gene, respectively. Regarding the method's specificity, no non-specific amplification was found when it was used to detect EML4-ALK fusion genes in leukocyte and plasma RNA samples from healthy volunteers. Among the 50 clinical samples, 47 ALK-FISH negative samples were also negative. Among 3 ALK-FISH positive samples, 2 cases were detected positive using this method, but another was not detected because of the failure of RNA extraction. Conclusion The proposed qRT-PCR assay for the detection of EML4-ALK fusion genes is rapid, simple, sensitive, and specific, which is deserved to be validated and widely used in clinical settings.

Quantitative Measurement of Cerebral Blood Flow in Enhanced Psedo-continuous Arterial Spin Labeling Perfusion Imaging in Patients with Intracranial Atherosclerotic Stenosis / 中国医学科学院学报

Objective To acquire cerebral blood flow (CBF) in patients with severe intracranial atherosclerotic stenosis with enhanced pseudo-continuous arterial spin labeling (e-pCASL) and compare it with the findings of dynamic susceptibility contrast-enhanced perfusion-weighted imaging (DSC PWI) and pseudo-continuous arterial spin labeling (pCASL). Methods A total of 39 consecutive patients with severe intracranial atherosclerotic stenosis were enrolled in this study. All these patients underwent e-pCASL, pCASL, and DSC PWI. Blood supply territory of the stenosed artery was outlined as region of interest (ROI) and a mirror ROI was applied. Ratios of CBF were calculated as value of ROI/value of mirror ROI. SNK variance analysis was conducted to compare the CBF values of three persufion methods. Factorial analysis of variance and Pearson were employed to analysis the difference and the correlation of e-pCASL CBF ratio, pCASL CBF ratio, and DSC PWI relative cerebral blood flow(rCBF) ratio. Results The e-pCASL CBF ratio, pCASL CBF ratio, and DSC PWI rCBF ratio were not significantly different (P=0.476). TTP showed the CBF ratios were not significantly different between the healthy side and diseased side in patients with severe intracranial atherosclerotic stenosis. ATT showed the correlations of pCASL CBF ratio and DSC PWI rCBF ratio were not affected by ATT. Conclusions e-pCASL with multiple-post labeling delay time and pCASL have good consistency with DSC PWI in the quantitative measurement of hypoperfusion pattern. As an accurate, simple, non-invasive, and repeatable technique, e-pCASL has good correlation with DSC PWI in the quantitative measurement of hypoperfusion pattern that is not affected by ATT.

Correlation of serum uric acid with bone mineral density and bone metabolic markers in middle-aged Chinese physical examination population / 第二军医大学学报

Objective To investigate the correlation of uric acid (UA) levels with bone mineral density (BMD) and serum bone metabolic markers in middle-aged Chinese physical examination population, so as to discuss the possible role of UA in bone metabolism. Methods A cross-sectional study with 214 middle-aged (45 to 65 years) Chinese physical examination participants was carried out. The correlation of UA levels with BMD and serum bone metabolic markers was observed. BMD values of the lumbar spine, total hip, femur neck and the whole body were measured by dual energy X-ray method. Bone turnover markers, including bone formation markers osteocalcin (OC) and procollagen type amino-terminal propeptide (PNP), bone resorption marker β-CrossLaps (β-CTX), 25-hydroxyvitamin D3 (25-OHD3), and parathyroid hormone (PTH) were measured by ECL immunoassay. Results After adjusting for multiple confounders, serum UA levels were found positively correlated with BMD at the lumbar spine, total hip and whole body (P≤0.001), negatively correlated with OC (P<0.01), and positively correlated with logPTH and log25-OHD3 (P=0.039, P=0.032). The participants were divided into high UA group (UA≥60 mg/mL) and low UA group (UA<60 mg/L) according to the serum UA level. OC, PNP and β-CTX were found significantly lower in the high UA group than in the low UA group (P<0.01). Then we divided the participants into three groups (T1: UA #x003C;47 mg/L,T2: 47 mg/L≤UA <60 mg/L; T3: UA≥60 mg/L) according to the serum UA level, and we found that the odds for osteoporosis and at least osteopenia increased by 41% and 158% in T1 group compared with in T3 group, respectively. Conclusion UA plays a protective role in bone metabolism of middle-aged Chinese population, and the relative comclusions need to be confirmed by further studies.

Role of Diffusion Weighted Magnetic Resonance Imaging at 3-T in Staging of Endometrial Cancer and Correlation to Histopathology.

Aim: To investigate the value of diffusion weighted imaging (DWI) at 3-T MR in staging of endometrial cancer and the correlation to histopathology. Study Design: A retrospective study. Place and Duration of Study: CT-MR Division, Qianfoshan Hospital Affiliated to Shandong University. Department of Radiology, Affiliated Hospital of Jining Medical College. From June 2013 to June 2014 Methodology: 30 patients with histologically proved endometrial cancers were analyzed retrospectively. The staging diagnosis of DWI was compared with pathologic results. The ADC values in different histologic types and different differentiated of endometrial cancers were also compared. P<0.05 was considered statistically significant. Results: The staging accuracy of DWI was 83.3%. The ADC value in 30 patients of endometrial cancer was (0.856±0.080) ×10-3 mm2/s. There was no statistically significant difference in different histologic types (t=1.093，P=0.284). In different differentiated endometrial cancers, there was significant difference (F=97.246，P=0.000). Conclusion: DWI has considerable value in staging of endometrial cancer. The ADC values can demonstrate the grade malignancy of tumors initially. So diffusion weighted sequences can be included in routine MR protocols for tumor assessment.

TNF-α gene polymorphisms and contents relationship between Han and Uygur in Xinjiang / 中国药学杂志

OBJECTIVE: To investigate the TNF-α gene promoter TNF-α-1031C/T, -863A/C, -857C/T, -308A/G polymorphism in difference between Han and Uygur, while gene polymorphism relationship with TNF-α contents.

Shang Ring, sleeve and conventional circumcisions for redundant prepuce and phimosis: A comparative study of 918 cases / 中华男科学杂志

<p><b>OBJECTIVE</b>To compare the clinical effects of conventional, sleeve and Shang Ring circumcisions in the treatment of redundant prepuce and phimosis.</p><p><b>METHODS</b>We reviewed the clinical data of 918 patients with redundant prepuce or phimosis, 279 treated by conventional circumcision, 354 by sleeve circumcision and 285 by Shang Ring circumcision. We documented the preoperative characteristics, intra-operative blood loss, operation time, 4-hour and 7-day postoperative visual analogue scores, surgeons' satisfaction, incision healing time, degrees of preputial edema, postoperative complications, patients' satisfaction with penile appearance and peri-operative cost, and compared them among the three groups.</p><p><b>RESULTS</b>Shang Ring circumcision significantly reduced the operation time and intra-operative blood loss as compared with conventional and sleeve circumcisions (P < 0.05). The postoperative incision healing time was (18.6 +/- 5.2) d in the conventional circumcision group, (11.4 +/- 3.7) d in the sleeve circumcision group and (20.3 +/- 5.7) d in the Shang Ring circumcision group, significantly shorter in the sleeve group than in the other two (P < 0.05). As for the surgeons' satisfaction, postoperative complications, degree of preputial edema and patients' satisfaction with penile appearance, sleeve circumcision showed similar effects to Shang Ring circumcision but significantly better than conventional circumcision (P < 0.05). The 7-day postoperative visual analogue score and peri-operative cost were significantly lower in the conventional and sleeve circumcision groups than in the Shang Ring group (P < 0.05).</p><p><b>CONCLUSION</b>Each of the three circumcision methods has its own advantages and disadvantages. The treatment decision should be individualized and based on a comprehensive consideration of the patients' age and economic status as well as surgeons' advice and surgical skills.</p>

Genetic characterization of a Chinese family with familial idiopathic pulmonary fibrosis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Idiopathic pulmonary fibrosis (IPF) is a chronic inflammatory interstitial lung disease with an unknown cause. Recent studies have shown that genetic factors play an important role in the pathogenesis of IPF.</p><p><b>METHODS</b>To explore the genetic background of patients with IPF, a candidate gene approach was employed to screen for mutations in seven genes among members with familial IPF in mainland of China.</p><p><b>RESULTS</b>Within six of the candidate genes, a total of 31 point mutations were identified. Among the missense mutations, the SFTPA1 exon 6 CAG > AAG (Gln238Lys) and SFTPB exon 2 CAC > CCC (His2Pro) mutations caused changes in the physical and chemical properties of amino acids. Each sequence alteration was identified in sporadic IPF patients, control specimens (pneumonia patients and healthy persons). Genotype frequencies and allele frequencies of codon 238 in exon 6 of SFTPA1 were noted significantly higher in patients with IPF than those in other two control subjects. The computational protein structure prediction by protein homology modeling confirmed differences in three-dimensional structure between mutant SFTPA1 and original SFTPA1.</p><p><b>CONCLUSIONS</b>Although the functions of the mutant candidate genes vary, these genes may ultimately result in damage to alveolar epithelial cells, initiating the progress of pulmonary fibrosis. In particular, while pathophysiological mechanisms need to be illustrated, the Gln238Lys missense variant of exon 6 in the SFTPA1 may have potential susceptibility in the development of IPF, which was shown in patients with sporadic IPF with a statistically higher frequency.</p>

Thin steel plate with thumbtack fixation in the treatment of massive presacral venous plexus hemorrhage / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Massive presacral venous plexus hemorrhage during radical resection of rectal carcinoma is rare, but when it occurs, bleeding can be uncontrollable, leading to death in some cases. Medical adhesive gauze sticking and packing and thumbtack compressive fixation are often used for hemostasis, but these methods are not effective in cases of uncontrollable massive hemorrhage. Therefore, identifying a practical, accurate, and reliable method of hemostasis in these cases is essential.</p><p><b>METHODS</b>Between January 2004 and December 2009, we treated 3 patients with massive presacral venous plexus hemorrhage during resection of rectal carcinoma by placing small, trimmed thin steel plates at the bleeding sites. The plates were fixed with a saddle-type application of thumbtacks.</p><p><b>RESULTS</b>Bleeding was successfully controlled in all 3 patients, and intestinal anastomosis was carried out after hemostasis. No complications were observed.</p><p><b>CONCLUSIONS</b>Application of a small, thin steel plate to the bleeding site with thumbtack fixation is a simple and effective method of hemostasis in patients with massive presacral venous plexus hemorrhage during resection of rectal carcinoma.</p>

Effects of thiamine and riboflavin on H_2O_2-induced DNA oxidative damage / 上海第二医科大学学报

Objective To explore the effects of thiamine and riboflavin on H2O2-induced DNA oxidative damage in human umbilical vein endothelial cell line ECV304.Methods ECV304 cells were incubated with 10,100,500,1000 mg/L of thiamine or 20,100,300,500 nmol/L of riboflavin for 24 h,and then oxidative damage of cells were induced by 25 mol/L H2O2 for 30 min.DNA damage was detected with single cell gel electrophoresis(SCGE)assay.ECV304 cells incubated without H2O2,thiamine and riboflavin were served as negative controls,and those incubated with H2O2 and without thiamine and riboflavin were served as positive controls.Results H2O2 induced DNA damage,and the indices of percent of DNA damage cells,percent of tail DNA,tail length and Olive tail moment were increased.The indices of cells pretreated with 10,100,500 mg/L of thiamine or 20,100,300 nmol/L riboflavin were significantly decreased(P0.05).Conclusion Proper supplementation of thiamine and riboflavin may decrease H2O2-induced DNA oxidative damage,while excess thiamine and riboflavin supplementation may be harmful to DNA and enhance the susceptibility to H2O2 potentially.

Study on the dynamics of IgG antibody in 311 patients with severe acute respiratory syndrome / 中华流行病学杂志

<p><b>OBJECTIVE</b>To detect the level and dynamic change of severe acute respiratory syndrome (SARS)-coronavirus-specific IgG antibody in conavalescent SARS patients, and to provide information for prevention and vaccine development.</p><p><b>METHODS</b>IgG antibody against coronavirus was detected by ELISA in the blood of 311 convalescent SARS patients for every 2 - 4 weeks. Stata 7.0 statistics software was used to analyse the results.</p><p><b>RESULTS</b>IgG antibody was detected positive on each testing of all the convalescent patients and its peak appeared 35 days after recovery. IgG antibody level showed a 35.8% decrease within one year.</p><p><b>CONCLUSION</b>Data showed that all the SARS convalescent patients had generated high level of specific IgG antibody against coronavirus in the early stage of recovery, but the antibody level declined along with the progress of convalescence, suggesting that the detection of the IgG antibody should go on until it disappeared.</p>

Detection of SARS-CoV RNA in stool samples of SARS patients by nest RT-PCR and its clinical value / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate of severe acute respiratory syndrome (SARS) convalescent stool shedding by RT-PCR.</p><p><b>METHODS</b>One hundred and three stool samples from 46 SARS patients were collected on May 16th, 20th, and 23rd, 2003. For each sample, RNA was extracted using commercial kit and 7 Nest RT-PCR using a 14-pair different SARS-associated coronavirus (SARS-CoV) special primers were carried out simultaneously.</p><p><b>RESULTS</b>Among these 46 SARS patients, 17 cases (37.0%) were stool SARS-CoV RT-PCR negative, and 29 cases (63.0%) were SARS-CoV RT-PCR positive. The duration of positive cases lasted (31.76 +/- 10.78) d (12-64 d). The longest stool shedding case in this study lasted 64 days. Two serial stool samples and for each sample 2 RT-PCR tests using different primers were positive in this case.</p><p><b>CONCLUSIONS</b>Our study observed longest stool shedding of SARS patients to be 64 days after initial onset of SARS. The average stool shedding was 32 days. Hence it is important to think highly of SARS convalescent patient stool sterilization.</p>