Role of melatonin receptor 1B gene polymorphism and its effect on the regulation of glucose transport in gestational diabetes mellitus / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Melatonin receptor 1B (MT2, encoded by the MTNR1B gene), a high-affinity receptor for melatonin, is associated with glucose homeostasis including glucose uptake and transport. The rs10830963 variant in the MTNR1B gene is linked to glucose metabolism disorders including gestational diabetes mellitus (GDM); however, the relationship between MT2-mediated melatonin signaling and a high birth weight of GDM infants from maternal glucose abnormality remains poorly understood. This article aims to investigate the relationship between rs10830963 variants and GDM development, as well as the effects of MT2 receptor on glucose uptake and transport in trophoblasts. TaqMan-MGB (minor groove binder) probe quantitative real-time polymerase chain reaction (qPCR) assays were used for rs10930963 genotyping. MT2 expression in the placenta of GDM and normal pregnant women was detected by immunofluorescence, western blot, and qPCR. The relationship between MT2 and glucose transporters (GLUTs) or peroxisome proliferator-activated receptor γ (PPARγ) was established by western blot, and glucose consumption of trophoblasts was measured by a glucose assay kit. The results showed that the genotype and allele frequencies of rs10830963 were significantly different between GDM and normal pregnant women (P<0.05). The fasting, 1-h and 2-h plasma glucose levels of G-allele carriers were significantly higher than those of C-allele carriers (P<0.05). Besides, the protein and messenger RNA (mRNA) expression of MT2 in the placenta of GDM was significantly higher than that of normal pregnant women (P<0.05). Melatonin could stimulate glucose uptake and GLUT4 and PPARγ protein expression in trophoblasts, which could be attenuated by MT2 receptor knockdown. In conclusion, the rs10830963 variant was associated with an increased risk of GDM. The MT2 receptor is essential for melatonin to raise glucose uptake and transport, which may be mediated by PPARγ.

Evaluation of colloidal gold method for detection of HIV-1 antibody in the urine / 上海预防医学

ObjectiveTo verify and promote the HIV antibody urine test in a demonstration zone for HIV prevention and control in Xinjiang， and to assess the sensitivity and specificity of the test and the willingness of the volunteers， providing a basis for evaluating and determining whether it was suitable for large-scale use in the region. MethodsStratified cluster sampling was used to select the respondents in a place in Xinjiang for questionnaire survey and sample collecting. Questionnaire results were statistically described， and multivariate logistic regression analysis was used to explore the influencing factors of willingness to use HIV-1 urine test. The results of blood ELISA antibody detection method were used as a reference to calculate the specificity， sensitivity and Kappa value of urinary HIV-1 antibody in the total population and different populations. ResultsA total of 2 504 volunteers were recruited for the urine self-testing. The sensitivity of HIV-1 antibody urine test in the total population was 94.73% （54/57）， the specificity was 100% （2 447）， the positive predictive value was 100% （54/54）， and the negative predictive value was 99.88% （2 447/2 450）. The specificity of each population group was 100% when comparing different populations. The test sensitivity was 100% in pregnant women， prostitutes and drug users， 50% （1/2） in MSM subjects， with a Kappa value of 0.796. The test sensitivity was 80% （8/10） in the volunteers， with a Kappa value of 0.878. In the satisfaction survey， 73.1% population was more likely to receive urinary rapid test than the blood fast test， 93.8% of the population was willing to recommend the rapid urinary detection to other people. More than 70% of the population was satisfied with the rapid urinary detection. The multivariate logistic regression analysis showed that age， degree of education， occupation， marital status， payment method of medical expenses， and income level were the influence factors of the purchase of urine fast reagent for the self-testing （P<0.05）. ConclusionUrinary HIV-1 antibody detection method has good reliability and public satisfaction. It is suitable for large-scale use in Xinjiang.

Research advances on thymosin β4 in promoting wound healing / 中华烧伤杂志

With the aging of population and the development of social economy, the incidence of chronic wounds is increasing day by day, while the incidence of burns and trauma remains at a high level, making wound repair an increasingly concerned area in clinical practice. Thymosin β4 is a naturally occurring small molecule protein in vivo, which is widely distributed in a variety of body fluids and cells, especially in platelets. Thymosin β4 has biological activities of promoting angiogenesis, anti-inflammation, anti-apoptosis, and anti-fibrosis, and has many important functions in wound repair. Thymosin β4 has been observed to promote the healing of various wounds, such as burns, diabetic ulcers, pressure ulcers. This paper will review the molecular structure, mechanism of wound healing promotion, pharmacokinetics, and clinical application of thymosin β4, aiming to introduce its potential in wound treatment and the shortcomings of current researches.

Effect of straight-line minimally invasive access cavity on the mechanical properties of maxillary first premolars: a finite element analysis / 中华口腔医学杂志

Objective: To investigate the effects of straight-line minimally invasive access cavity on the mechanical properties of endodontically treated maxillary first premolars using finite element analysis. Methods: Micro-CT data of twenty maxillary first premolars were collected for three-dimensional reconstruction. Three access cavities, including the conventional access cavity (ConvAC), the truss access cavity (TrussAC) and the straight-line minimally invasive access cavity (SMIAC), as well as the root canal treatment procedure, were simulated in all the 20 reconstruction samples of three-dimensional models, respectively. The peak von Mises stress on the cervical area of each model, as well as the stress distribution under vertical and oblique loading circumstances, were subsequently determined by using finite element analysis. Results: In comparison to the stresses of ConvAC [buccal cervical (BC): (188.7±13.4) MPa, palatal cervical (PC): (200.9±25.7) MPa], the stresses of TrussAC [BC: (146.0±12.9) MPa, PC: (167.6±15.9) MPa] (t=9.01, P<0.001; t=4.59, P<0.001) and SMIAC [BC: (142.6±13.7) MPa, PC: (168.1±17.4) MPa] (t=9.64, P<0.001; t=3.76, P=0.004) significantly reduced the peak von Mises stress on the cervical area of the maxillary first premolars after root canal treatment. Under vertical loading conditions, SMIAC also reduced the central tendency of stresses on the occlusal surface, cervical area and root. In the case of oblique loading conditions, similar results were observed. Under both loading conditions, there was no significant difference in the peak von Mises stress on the cervical area of the maxillary first premolar between TrussAC and SMIAC groups. Conclusions: The design of SMIAC could preserve the mechanical properties of the maxillary first premolar following root canal treatment, which might have certain clinical feasibility.

Two different techniques combined with MIS-TLIF in the treatment of degenerative lumbar spondylolisthesis:a case-control study / 中国骨伤

OBJECTIVE@#To analyze the difference in clinical efficacy of minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) under Quadrant channel system combined with microscope and percutaneous pedicle screw in the treatment of degenerative lumbar spondylolisthesis.@*METHODS@#A total of 114 patients with single-segment degenerative lumbar spondylolisthesis from June 2015 to February 2019, were divided into three groups according to the surgical methods, such as the MIS-TLIF under the microscope surgery group ( microscope group), MIS-TLIF combined with percutaneous pedicle screw technique surgery group(percutaneous group) and posterior lumbar interbody fusion surgery group (open group). In the microscope group, there were 12 males and 26 females, aged from 42 to 83 years with an average of (63.29±9.09) years. In the percutaneous group, there were 16 males and 22 females, aged from 45 to 82 years with an average of (63.37±7.50) years. In the open group, there were 12 males and 26 females, aged from 51 to 82 years with an average of (63.76±8.21) years. The general conditions of operation, such as operation time, intraoperative blood loss, postoperative drainage, length of surgical incision, frequency of intraoperative fluoroscopy and postoperative time of lying in bed were recorded to analyze the differences in surgical related indicators. Visual analogue scale (VAS) of waist and leg pain in preoperative and postoperative period (3 days, 3 months, 6 months and 12 months) were recorded to evaluate pain remission;Oswestry Disability Index(ODI), Japanese Orthopaedic Association (JOA) score were recorded to evaluate the recovery of waist and leg function on preoperative and postoperative 12 months. The lumbar spondylolisthesis rate and intervertebral height at 12 months after operation were recorded to evaluate the reduction of spondylolisthesis. The Siepe intervertebral fusion standard was used to analyze the intervertebral fusion rate at 12 months after operation.@*RESULTS@#①All 114 patients were followed up more than 1 year, and no complications related to incision infection occurred. In the microscope group, there was 1 case of subcutaneous effusion 8 days after operation. After percutaneous puncture and drainage, waist compression, and then the healing was delayed. In the percutaneous group, 2 cases of paravertebral muscle necrosis occurred on the side of decompression, and the healing was delayed after debridement. In open group, there was 1 case of intraoperative dural tear, which was packed with free adipose tissue during the operation. There was no postoperative cerebrospinal fluid leakage and other related complications.① Compared with microscope group, percutaneous group increased in operation time, intraoperative blood loss, postoperative wound drainage, surgical incision length, intraoperative fluoroscopy times, and postoperative bed rest time. In open group, intraoperative blood loss, postoperative wound drainage, surgical incision length, and postoperative bed rest time increased, but the intraoperative fluoroscopy time decreased. Compared with percutaneous group, the intraoperative blood loss, wound drainage, surgical incision length, and postoperative bed rest time in open group increased, but operative time and the intraoperative fluoroscopy time decreased(P<0.05). ②ODI and JOA scores of the three groups at 12 months after operation were improved compared with those before operation (P<0.05), but there was no significant difference between the three group(P>0.05). ③Compared with microscope group, the VAS of low back pain in percutaneous group increased at 3 days after operation, and VAS of low back pain in open group increased at 3 days, and 12 month after operation. Compared with percutaneous group, the VAS low back pain score of the open group increased at 3 months after operation (P<0.05). ④ The lumbar spondylolisthesis rate of the three groups of patients at 12 months afrer operation was decreased compared with that before operation(P<0.05), and the intervertebral heigh was increased compared with that before operation(P<0.05), however, there was no significant difference among three groups at 12 months afrer operation(P>0.05). ⑤ There was no significant difference between three groups in the lumbar fusion rate at 12 months afrer operation(P>0.05).@*CONCLUSION@#The MIS-TLIF assisted by microscope and the MIS-TLIF combined with percutaneous pedicle screw are safe and effective to treat the degenerative lumbar spondylolisthesis with single-segment, and the MIS-TLIF assisted by microscope may be more invasive, cause less blood loss and achieve better clinical efficacy.

Efficacy and safety of Di-Tan Decoction for treating post-stroke neurological disorders: a systematic review and Meta-analysis of randomized clinical trials / 中国天然药物

The management of post-stroke complications plays an important role in the quality of life. Di-Tan Decoction (DTD; ) is a widely used traditional Chinese medicine. This study incorporated systematic review and meta-analysis to evaluate the efficacy of DTD in post-stroke neurological disorders. Randomized clinical trials (RCTs) were searched from English, Chinese and Korean electronic medical databases, by including the keywords "Di-Tan Tang", "Di-Tan Decoction", "Scour Phlegm Decoction", "stroke", and "RCT. Each RCT included control (placebo, conventional therapy, or Western medicine) and experimental (DTD treatment) groups. For patients inflicted with stroke for 1-6 weeks, the outcomes of post-stroke neurological disorders were measured by scales for post-stroke symptoms and were classified as "completely healed", "markedly effective", "effective" and "ineffective". Totally, 11 RCTs (n = 490 controls and n = 502 DTD subjects) were selected from 210 articles identified in the initial search. A meta-analysis of evaluation criteria in post-stroke symptoms revealed that the overall odds ratio (ORs) for alleviating post-stroke neurological disorders were 0.30-fold lower (95% CI = 0.21-0.43) in the DTD group than the control (Western medicine) group (P < 0.000 01). Moreover, regardless of the type of stroke diagnostic scale applied (including NFA, HDS, and NIHSS), the overall post-stroke symptoms determined were less severe in the DTD group (n = 219) than the control group (n = 217). No adverse effects of DTD were observed in the 11 RCTs reviewed. All 11 studies used an appropriate method for randomization of subjects to evaluate the risk of bias (ROB), and 7 studies included allocation concealment as well as blinding of patients and practitioners. High-risk ROB was included in 6 RCTs. No significant publication bias was derived from the funnel plot. Our results indicate that the administration of DTD alone, and DTD in combination with Western medicine, exert greater efficacy for post-stroke complication therapy, than Western medicine administered alone. More rigorous and regulated studies are required to confirm the therapeutic efficacy of DTD for post-stroke neurological disorders. disorders.

Bifidobacterium combined with cationic lipid nanoparticles with liquid perflurocarbon for improving HIFU ablation effect: Experimental study / 中国介入影像与治疗学

Objective: To investigate the influence of bifidobacterium combined with cationic lipid nanoparticles with liquid fluorocarbon on HIFU ablation for tumor-bearing mice. Methods: Bifidobacterium was cultured, cationic lipid nanoparticles with liquid fluorocarbon were prepared, and the connection ratio was examined in vitro. Mice models of human breast cancer MDA-MB231 cells were established. A total of 48 tumor-bearing mice were randomly divided into 4 groups (each n=12). Different substances were injected through the tail vein twice (two days apart). Tumor-bearing mice in group A (PBS group) were injected with phosphate buffer (PBS) twice, in group B (bifidobacterium group) were injected with bifidobacterium before PBS injection, in group C (cationic lipid nanoparticles) with PBS before cationic lipid nanoparticles injection and in group D (bifidobacterium+cationic lipid nanoparticle group) with bifidobacterium before cationic lipid nanoparticles injection. Twenty-four hours after the completion of the second injection, HIFU irradiation was performed on the tumor tissue of tumor-bearing mice, and the changes between pre- and post-ablation gray scale of the tumor tissue were analyzed. Histological examination was performed 1 h before HIFU irradiation and 1 day after irradiation, respectively. The tumor targeting of bifidobacterium was observed, and the coagulative necrotic volume of tumor tissues and energy efficiency factor (EEF) of HIFU ablation were measured. Statistical analysis was performed to compare the differences among 4 groups. Results: Gram-stained bifidobacterium longum was manifested as blue-violet long rod with a surface potential of -29 mV. The cationic lipid nanoparticles were spherical and evenly distributed with average particle diameter of (280.21±60.20)nm and a surface potential of 25 mV. The differences of gray scale change (F=143.40), coagulative necrotic volume (F=243.20) and EEF (F=56.33) were statistically significant among 4 groups (all P<0.001). Gray value change and coagulative necrotic volume gradually increased in group A, B, C and D (pairwise comparison: All P<0.05), while EEF trended from high to low in group A, B, C and D (pairwise comparison: All P<0.05). There was no bifidobacterium in heart, liver, spleen, lung and kidney of tumor-bearing mice among 4 groups nor in tumors of group A and C. A quantity of bifidobacterium was found in tumor tissue of group B and D. Conclusion: Bifidobacteriaum combined with cationic lipid nanoparticles with liquid fluorocarbon can enhance the ablation effect of HIFU ablation on tumor tissue in tumor-bearing mice.

Mechanism of Gardenia jasminoides against cholestasis based on network pharmacology / 中国中药杂志

To screen the active ingredients of Gardenia jasminoides and potential targets,and investigate the mechanisms against cholestasis based on network pharmacology technology. Twenty-one active components of G. jasminoides were retrieved and the target sites were screened by using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform( TCMSP). Cytoscape3. 2. 1 was used to construct the component-target network. Two hundred and eight targets related to cholestasis were searched and screened through Dis Ge NET,KEGG and OMIM databases. The key targets of G. jasminoides components and cholestasis were integrated and screened,and the component-target-disease network was constructed with Cytoscape 3. 2. 1 software to screen out the core network whose freedom degree was greater than the average value. The Clue GO plug-in of Cytoscape 3. 2. 1 software was used to analyze the biological processes and pathway enrichment of G. jasminoides in regulation of cholestasis. GO biological process analysis revealed 17 biological processes,involving 3 signaling biological processes related to cholestasis,i.e. acute inflammatory response,positive regulation of reactive oxygen species metabolic process,and nitric oxide biosynthetic process. KEGG-KEEG-305 terms and REACTOME pathways analysis revealed 17 regulatory pathways,involving 4 signaling pathways related to cholestasis,i.e. metabolism of xenobiotics by cytochrome P450,nuclear receptor transcription pathway,GPVI-mediated activation cascade and platelet activation. It was found that aqueous extract of G. jasminoides could improve serum biochemical abnormalities in ANIT-induced cholestasis rats. Aqueous extract of G. jasminoides could decrease the protein and mRNA expression levels of ESR1 in liver tissues,and increase the protein and mRNA expression levels of PPARG,NOS2,F2 R,NOS3,and NR3 C1. To sum up,the possible mechanisms of G. jasminoides against cholestasis may be related with the above three processes and four pathways.

The dosimetric effect of inconsistency of bladder filling states between CT simulation and IMRT treatment for prostate cancer patients / 中华放射医学与防护杂志

Objective To analyze the dosimetric effect of inconsistent bladder filling states between the CT simulation and treatment for prostate cancer patients undergoing intensity-modulated radiotherapy (IMRT).Methods A total of 42 prostate cancer patients treated with IMRT were selected.After vacuum pad immobilization and simulation CT scan,the delineation of targets and organs-at-risk (OARs),treatment planning and dose calculation were performed on treatment planning system (TPS).The cone-beam-CT (CBCT) acquired before the first treatment was registered to planning CT,on which the target contours were duplicated and OARs were delineated.After dose recalculation on the CBCT using the same plan,the dosimetric differences on the CT and CBCT were compared,including mean dose of the planning target volume (PTV),homogeneity index (HI),conformity index (CI);the mean dose,V30,V40,V50,V60,and V65 of bladder and rectum respectively.Results Relative to the bladder volumes at simulation,the patients were divided into two groups with larger (15 cases) or smaller (27 cases) bladders at the first treatment.Comparing the parameters obtained from simulation CT with that from CBCT,the differences of the following parameters were of statistical significance:the bladder volume,PTV HI,PTV CI in both groups (t =6.838,-4.372,-3.553,-3.462,6.380,5.037,P＜ 0.05),the bladder V30,V40,V50,V60,V65(t=-5.004,-4.092,-3.124,-2.707,-2.489,P ＜0.05) and rectal V40,V50,V60,V65,mean dose in the group with smaller bladders (t=-2.946,-2.643,-2.426,-3.127,-2.530,P ＜ 0.05),and the bladder V30,V40,V50 and mean dose in group with larger bladders (t =5.107,4.204,3.777,4.155,P＜0.05).Conclusions For prostate cancer patients undergoing IMRT,the inconsistent bladder filling states between the planning and treatment will cause disimetric differences of targets and OARs.

Effect of -induced changes in tumor tissue acoustic properties on efficacy of high-intensity focused ultrasound ablation / 南方医科大学学报

OBJECTIVE@#To investigate the effects of on the acoustic characteristics of tumor tissue and how such acoustic changes affect the efficacy of high-intensity focused ultrasound (HIFU) ablation in nude mice.@*METHODS@#Forty mice bearing human breast cancer cell (MDA-MB-231) xenograft were randomized into experimental group (=20) and control group (=20) for intravenous injection of suspension (200 μL, 4 × 10 cfu/mL) and PBS (200 μL) for 3 consecutive days, respectively. Before and at 3 and 7 days after the first injection, shear wave elastography was used to evaluate the hardness of the tumor tissue. On day 7 after the first injection, 10 mice from each group were sacrificed and the sound velocity and sound attenuation of the tumor tissues were measured. The changes in the collagen fibers in the tumors were evaluated using Masson staining, and neovascularization in the tumor was assessed with immunohistochemistry for platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31). The remaining 10 tumor-bearing mice in each group were subjected to HIFU ablation, and the ablation efficiency was evaluated by assessing the changes in irradiation gray values, coagulative necrosis volume, energy efficiency factor (EEF) and irradiation area and by pathological examination with HE staining.@*RESULTS@#In the experimental group, the collagen fibers in the tumor tissues were strong and densely aligned, and the tumors contained fewer new blood vessels showing strip-or spot-like morphologies. In the control group, the collagen fibers in the tumors were thin and loosely arranged, and the tumors showed abundant elongated or round new blood vessels. colonized in the tumor 7 days after the injection, and the tumor hardness was significantly greater in the experimental group than in the control group (=0.01); the acoustic velocity (=0.001) and the acoustic attenuation (=0.000) of the tumor tissues were also greater in the experimental group. HIFU irradiation resulted in significantly greater changes in the gray scale of tumor (=0.0006) and larger coagulative necrosis volume (=0.0045) in the experimental group than in the control group, and the EEF was significantly smaller in the experimental group (=0.0134).@*CONCLUSIONS@# can cause changes in collagen fiber content, acoustic velocity and attenuation in the tumor tissue and reduce the EEF of HIFU irradiation, thereby improving the efficacy of HIFU irradiation.

Effect of geniposidic acid on SHP-LRH-1 signaling pathway in cholestasis rats / 中南大学学报(医学版)

To explore the effect of geniposidic acid (GPA) on the signal pathway of small heterodimer dimer receptor (SHP) and liver receptor homologue 1 (LRH-1) in cholestasis rats induced by alpha-naphthalene isothiocyanate (ANIT).
 Methods: Fifty SD rats were randomly divided into five groups: a blank group, an ANIT group, an ANIT+GPA (100 mg/kg) group, an ANIT+GPA (50 mg/kg) group, and an ANIT+GPA (25 mg/kg) group (n=10 in each group). The GPA were intragastrically given to rats for 10 days, and the control group and the ANIT group were given normal saline. At the eighth day of administration, all rats except the blank group were given 65 mg/kg ANIT once until the tenth day. After the last administration, serum total cholesterol (TC), triglyceride (TG) and total bile acids (TBA) were measured. The primary hepatocytes (RPH) were isolated from normal rats and cultured. The cells were divided into a blank group, an ANIT (40 μmol/L) group, an ANIT (40 μmol/L)+GPA (4.00 mmol/L) group (A4.00G group), an ANIT (40 μmol/L)+GPA (1.00 mmol/L) group (A1.00G group), and an ANIT (40 μmol/L)+GPA (0.25 mmol/L) group (A0.25G group). The mRNA transcription levels of SHP and cholesterol 7 alpha hydroxylase (CYP7A1) in RPH were detected by real-time-PCR, and the protein levels of SHP and CYP7a1 were detected by Western blotting. In the LRH-1 silence experiment, the RPH were divided into a blank group, a negative transfection group, a siRNA-LRH group (ZR group), a siRNA-LRH+GPA (4.00 mmol/L) group (ZR4.00G group), a siRNA-LRH+GPA (1.00 mmol/L) group (ZR1.00G group) and a siRNA-LRH+GPA (0.25 mmol/L) group (ZR0.25G group). The protein and mRNA levels of SHP, CYP7a1, LRH-1 were detected. In the over-expression experiment, the RPH were also divided into a blank group, a negative transfection group, a LRH-1 over-expression plasmid group (OE group), a LRH-1 over-expression plasmid+GPA (4.00 mmol/L) group (OE4.00G group), a LRH-1 over-expression plasmid+GPA (1.00 mmol/L) group (OE1.00G group), and a LRH-1 over-expression plasmid+GPA (0.25 mmol/L) group (OE0.25G group). The protein and mRNA levels of SHP, CYP7a1 and LRH-1 were detected.
 Results: Compared with the blank control group, TC and TBA were significantly increased (both P<0.01) in the ANIT group, but there was no difference in TG; compared with the ANIT group, the contents of TC and TBA in the AG100 and AG50 groups were significantly reduced (all P<0.01). Compared with the blank control group, the proteins and mRNA levels of SHP were significantly decreased (P<0.01), while CYP7a1 were dramatically increased (P<0.01) in the ANIT group; compared with the ANIT group, the proteins and mRNA levels of SHP in the A4.00G group and the A1.00G group were significantly increased (both P<0.01), while the levels of CYP7a1 proteins and mRNA levels were evidently decreased in the A4.00G and A1.00G groups (both P<0.01). Compared with the negative transfection group, the proteins and mRNA levels of CYP7a1 and LRH-1 were dramatically restrained (all P<0.01), while there was no change in SHP in the ZR group; compared with the ZR group, the proteins and mRNA levels of SHP were significantly increased (all P<0.01), while LRH-1 and CYP7a1 were not changed in the ZR4.00G, ZR1.00G and ZR0.25G groups. Compared with the negative transfection group, the protein and mRNA levels of CYP7a1 and LRH-1 were significantly suppressed in the OE group (all P<0.01). Compared with the OE group, the protein and mRNA levels of SHP were evidently increased in the OE4G and OE1G groups (all P<0.01), while LRH-1 and CYP7a1 were not changed in the OE4G, OE1G and OE0.25G groups.
 Conclusion: The over-expression of LRH-1 in RPH can up-regulate the mRNA and protein levels of CYP7a1. GPA can improve the biochemical and liver pathology of ANIT-induced cholestasis rats, which may be related to the decrease of CYP7a1 by activating SHP through LRH-1 in RPH.

Preparation of annonaceous acetogenins nanosuspensions using poloxamer 188 as a stabilizer and their in vitro and in vivo investigation / 药学学报

Annonaceous acetogenins (ACGs) are effective part extracted and separated from Annona squamosa seeds, they have good antitumor activity against a variety of tumor cells. However, the solubility of ACGs is poor with serious toxic and side effects, which greatly limits their application in clinical practice. In this study poloxamer 188 (P188) was selected as a drug carrier or a stabilizer to prepare ACGs nanosuspensions (ACGs-NSps) using anti-solvent precipitation. The nanosuspensions were examined via dynamic light scattering (DLS) method to examine size of the nanosuspensions. Transmission electron microscopy was used to observe their morphology. HPLC assay was used to measure their drug loading content and the in vitro drug release. The stability of ACGs-NSps at room temperature, in various physiological media and plasma, and the hemolytic test and lyophilization were all investigated. MTT assay was performed to study the cytotoxocity of ACGs-NSps against four tumor cell lines. 4T1 bearing tumor model was used to assess their in vivo antitumor therapeutic efficacy. The obtained ACGs-NSps were spherical, the average particle size was 169.4±1.25 nm, the polydispersity index (PDI) value was 0.130±0.020, the zeta potential was -19.8 mV and the drug loading content was 48.18%. ACGs-NSps were stable at room temperature for at least 15 days. They could be lyophilized in the presence of 0.5% glucose and 2.0% P188. ACGs-NSps showed sustained in vitro drug release, and the cumulative drug release reached 80.82% within 144 hours. ACGs-NSps maintained their particle size in various physiological media, and plasma with no hemolysis and then met demands of both oral and intravenous administration. In contrast to free ACGs, ACGs-NSps displayed significantly higher cytotoxicity against 4T1 (IC50, 0.892±0.124 μg·mL-1 vs 2.495±0.108 μg·mL-1, P 50, 0.747±0.051 μg·mL-1 vs 2.204±0.064 μg·mL-1, P 50, 2.265±0.081 μg·mL-1 vs 4.159±0.071 μg·mL-1, P 50, 0.473±0.024 μg·mL-1 vs 1.196±0.022 μg·mL-1, P in vivo study demonstrated that the daily oral administration of ACGs-NSps (3 mg·kg-1) resulted in higher tumor inhibition rate compared to ACGs/oil solution (67.23% vs 53.11%), comparable to the intravenous injection of 0.5 mg·kg-1 ACGs-NSps every other day (70.34%). Nanosuspensions effectively solved the problem of ACGs insolubility and difficulty in drug delivery. Using P188, a pharmaceutic adjuvant approved by FDA for iv injection, the resultant ACGs-NSps appear promising as an anti-tumor drug that can be used in clinic.

Study on the structure of an unknown impurity in carboplatin injection and the relationship with the excipient / 药学学报

The study was designed to establish a 2D UPLC-QTOF method to extrapolate the structure of an unknown substance in carboplatin injection and its relationship with the excipient. By using phenyl-hexyl column (250 mm×4.6 mm, 5 μm) with mobile phase consisting of tetrabutylammonium sulfate buffer (pH 7.5) and acetonitrile in gradient elution mode, an unknown impurity in carboplatin injection was found and quantitatively determined. Then a 2D UPLC-QTOF, HSS T3 column (100 mm×2.1 mm, 1.7 μm) was employed to confirm the molecular weight and the structure of the unknown impurity (electrospray ionization source, positive ion mode, MSE mode) with mobile phase consisting of 0.1% formic acid and acetonitrile. The relationship among impurities, API and excipient was investigated by accelerated stability test with ICP-MS/MS, ICP-AES. Results showed that disodium edetate in the formulation interacted with carboplatin producing an unknown impurity containing platin, and induced the increase of 1,1-cyclobutanedicarboxylic acid. The research should be done on the rationality of the addition of disodium edetate in such injections containing heavy metals.

Resting-state functional MRI study at the baseline in mild cognitive impairment converting to Alzheimer's disease / 中华放射学杂志

Objective To explore the features of resting state functional magnetic resonance imaging (rs-fMRI) in the patients with mild cognitive impairment (MCI) after during the process of converting to Alzheimer's disease (AD) dementia. To study the correlation of the brain function imaging and neuropsychological scores in converted MCI subjects with the purpose of finding the potential functional biomarkers which may predict the conversion of MCI to AD dementia in short term using resting state functional MRI. Methods Twenty-seven patients with MCI and 31 age, gender and years of education matched normal controls (NC) were enrolled in this study and neuropsychological assessment and rs-fMRI data were acquired respectively at the baseline and follow-up. Functional connectivity strength (FCS) analyses were used to assess the functional differences among the groups of MCI-converters (MCI-c) , MCI-non converters (MCI-nc) and NC. Variance analyses were used to compare the group differences in age, years of education and each neuropsychological assessment. In addition, Chi-squared test was used to compare group differences in gender. Then, Kruskal-Wallis test was used to compare group differences in the interval time of twice data collection. Group differences in FCS values were analyzed by general linear model. Finally, correlation analyses were used to evaluate the relationships between the FCS values of the brain regions with group differences and neuropsychological assessment scores in MCI patients. Results (1) Significant group differences of FCS among the MCI-c, MCI-nc and NC groups were observed in bilateral angular gyri, bilateral orbitofrontal cortex, right precentral gyrus, left paracentral lobule, left precuneus, right fusiform, right middle occipital gyrus, right superior occipital gyrus, left cerebellum. (2) The MCI-c showed decreased FCS in bilateral angular gyri, right middle occipital gyrus, right superior occipital gyrus, right inferior occipital gyrus, right fusiform, left precuneus, and left paracentral lobule, as compared to MCI-nc, the cluster was 149, 114, 186, 56, 48, 33, 38 and 102 voxels, respectively;P<0.05, respectively. The correlation analysis showed that the FCS values of the right angular gyrus were negative correlated with the MMSE scores (r=-0.561, P=0.017) . Conclusions This study revealed that the comparison of rs-fMRI imaging data between MCI-c and MCI-nc at baseline is of great benefits in analysing the imaging characteristics of patients during converting from MCI to AD. The feature of FCS in rs-fMRI in right angular gyrus might serve as early indicators for the dysfunction and progression from MCI to AD.

Resting-state functional MRI study at the baseline in mild cognitive impairment converting to Alzheimer's disease / 中华放射学杂志

Objective To explore the features of resting state functional magnetic resonance imaging (rs-fMRI) in the patients with mild cognitive impairment (MCI) after during the process of converting to Alzheimer's disease (AD) dementia. To study the correlation of the brain function imaging and neuropsychological scores in converted MCI subjects with the purpose of finding the potential functional biomarkers which may predict the conversion of MCI to AD dementia in short term using resting state functional MRI. Methods Twenty-seven patients with MCI and 31 age, gender and years of education matched normal controls (NC) were enrolled in this study and neuropsychological assessment and rs-fMRI data were acquired respectively at the baseline and follow-up. Functional connectivity strength (FCS) analyses were used to assess the functional differences among the groups of MCI-converters (MCI-c) , MCI-non converters (MCI-nc) and NC. Variance analyses were used to compare the group differences in age, years of education and each neuropsychological assessment. In addition, Chi-squared test was used to compare group differences in gender. Then, Kruskal-Wallis test was used to compare group differences in the interval time of twice data collection. Group differences in FCS values were analyzed by general linear model. Finally, correlation analyses were used to evaluate the relationships between the FCS values of the brain regions with group differences and neuropsychological assessment scores in MCI patients. Results (1) Significant group differences of FCS among the MCI-c, MCI-nc and NC groups were observed in bilateral angular gyri, bilateral orbitofrontal cortex, right precentral gyrus, left paracentral lobule, left precuneus, right fusiform, right middle occipital gyrus, right superior occipital gyrus, left cerebellum. (2) The MCI-c showed decreased FCS in bilateral angular gyri, right middle occipital gyrus, right superior occipital gyrus, right inferior occipital gyrus, right fusiform, left precuneus, and left paracentral lobule, as compared to MCI-nc, the cluster was 149, 114, 186, 56, 48, 33, 38 and 102 voxels, respectively;P<0.05, respectively. The correlation analysis showed that the FCS values of the right angular gyrus were negative correlated with the MMSE scores (r=-0.561, P=0.017) . Conclusions This study revealed that the comparison of rs-fMRI imaging data between MCI-c and MCI-nc at baseline is of great benefits in analysing the imaging characteristics of patients during converting from MCI to AD. The feature of FCS in rs-fMRI in right angular gyrus might serve as early indicators for the dysfunction and progression from MCI to AD.

Predictive value for adverse cardiac events of left ventricular diastolic function measured by gated myocardial perfusion imaging / 中华核医学与分子影像杂志

Objective To study the predictive value for adverse cardiac events (ACE) of left ventricular diastolic function measured by G-MPI. Methods Patients assessed by 2 days rest-stressed G-MPI during March 2012 to May 2013 in Beijing Hospital were collected and observed for the cumulative survival rate without ACE after G-MPI. ACE included cardiac death, non-fatal MI and late revascularization (60 d after the examination). Using quantitative gated SPECT (QGS) to get the LVEF and left ventricular peak filling rate (PFR). Using 17 segments, 5-point scoring system to get the summed stress score (SSS). Cox regression analysis was used to identify the independent predictors for ACE, and Kaplan-Meier method was used to investigate the cumulative survival rate without ACE.χ2 test was also used. Results A total of 11 patients who underwent early revascularization (within 60 d after G-MPI) were excluded and 139 patients (76 males, 63 females; average age 68.73 years) were assigned to different groups for outcome analysis, and 9 (6.5%, 9/139) patients had ACE in the whole group. Cox regression analysis showed that SSS, LVEF, PFR were the independent predictors for ACE (all P<0.05). Patients with PFR<2.1 EDV/s had a higher incidence of ACE than those with PFR≥2.1 EDV/s (14.3%(7/49) vs 2.2%(2/90), χ2=7.63, P<0.05). Kaplan-Meier survival analysis showed that the cumulative survival rate without ACE was lower in patients with PFR<2.1 EDV/s than that in patients with PFR≥2.1 EDV/s (67.7% vs 95.0%), and lower in patients with LVEF<50% than that in patients with LVEF≥50%(32.0% vs 90.8%), and also lower in patients with SSS≥8 than those with SSS<8(62.0% vs 94.7%; χ2 values: 11.92,11.27, 10.40, all P<0.01).Combining PFR with SSS and LVEF respectively, Kaplan-Meier survival analysis showed that the cumulative survival rate without ACE in patients with LVEF≥50% was higher than that in patients with LVEF<50% when PFR<2.1 EDV/s (76.7% vs 30.8%), and also higher in patients with SSS<8 than that in patients with SSS≥8 when PFR≥2.1 EDV/s (100% vs 72.2%; χ2 values: 7.14, 13.09, both P<0.01). Conclusion PFR of left ventricular diastolic function measured by G-MPI is one of the independent predictors for ACE, and it could effectively improve the predictive value for ACE if combined with LVEF and SSS.

Evaluation of ketamine-induced cerebral protection in mice with traumatic brain injury by magnetic resonance imaging / 中华麻醉学杂志

Objective To evaluate ketamine-induced cerebral protection in mice with traumatic brain injury (TBI) by magnetic resonance imaging (MRI).Methods Thirty-two pathogen-free healthy male C57BL/6 mice,aged 8 weeks,weighing 26-30 g,were divided into 4 groups using a random number table:control group (group C,n=7),ketanine group (group K,n=7),TBI group (n=9) and TBI plus ketamine group (group TBI+K,n =9).TBI was produced with a pneumatically driven controlled cortical impact device.Ketamine 150 mg/kg was intraperitoneally injected at l h after operation in TBI+K and K groups,while the equal volume of normal saline was given instead in TBI and C groups.Open field test was conducted at 24 h,72 h and 7 days after operation.The animals in TBI and TBI+K groups were scanned by T1-weighted MRI at 6,24 and 72 h after operation,the animals in C and K groups were scanned by MRI at 24 h after operation,and the development of cerebral edema was observed.Results MRI scan showed no cerebral edema in C and K groups,and different degrees of cerebral edema were found in TBI and TBI+K groups.Compared with group C,the locomotor distance was significantly shortened at 24 and 72 h after operation in group TBI (P＜0.05).Compared with group TBI,the size of cerebral edema was significantly decreased,and the locomotor distance was prolonged at 24 and 72 h after operation in group TBI+K (P＜0.05 or 0.01).Conclusion MRI method further clarifies that ketamine can produce cerebral protection to some extent in mice with TBI.

Routine semen parameters and sperm morphological index of infertile males with partial globozoospermia / 中华男科学杂志

Objective@#To investigate the routine semen parameters and sperm morphological indexes of the patients with partial globozoospermia (PGZ).@*METHODS@#We included in this study 100 infertile males with PGZ and another 180 non-PGZ infertile men as controls. According to the proportion of round-headed sperm (RHS) in the semen, we classified the PGZ males into five subgroups: 25%－40%, 41%－55%, 56%－70%, 71%－85%, and 86%－99% RHS. We obtained sperm concentration, total sperm motility, the percentage of progressively motile sperm, teratozoospermia index (TZI), and sperm deformity index (SDI) from the subjects and compared them among different groups.@*RESULTS@#Statistically significant differences were found between the PGZ patients and non-PGZ controls in total sperm motility (［35.76±24.88］% vs ［62.03±10.20］%, P0.05), sperm concentration (［46.01±40.38］ vs ［54.00±25.15］ ×106/ml, P>0.05), or TZI (1.35±0.11 vs 1.34±0.54, P>0.05). There were also significant differences among the five PGZ subgroups in total sperm motility, progressive sperm motility, normal sperm morphology, TZI, and SDI (P0.05). Morphologically, the sperm head changed from heterogeneous to homogeneous with the increased proportion of round-headed sperm.@*CONCLUSIONS@#Different proportions of round-headed sperm are closely related to routine semen parameters and sperm morphological index in PGZ patients, which can help clinicians choose the proper assisted reproductive technology and predict the rate of fertilization for infertile males.

Research and implementation of gray-scale blood flow imaging system of high frequency ultrasound / 国际生物医学工程杂志

Objective To study the method of gray-scale blood flow imaging and image processing in condition of high frequency ultrasound,and the implementation of the system.Methods On the base of research of scattered signals of red blood cells in high frequency ultrasound,20 MHz ultrasound mechanical and linear scanning probe was used to transmit a number of pulses on a scan line.Pulse-echo subtraction method was used to obtain the blood flow information.At the end,simulated blood vascular was used to conduct flow imaging,and the obtained images were analyzed.Results Experiment results showed that clear blood flow images were obtained using this system.The noise from perivascular tissue could be filtered and the signals from blood flow could be enhanced after image processing.Conclusions In the detection of superficial blood vessel,blood flow signals can be obtained even using single pulse emitting via high frequency ultrasound.The blood flow imaging system can be implemented after image processing.

Investigation on influence factors of gernal surgeon growth / 中华医学教育探索杂志

Objective To investigate the general surgeon growth time, and to probe into the factors affecting the surgeon growth. Methods 72 surgeons who worked more than 15 years in the field of general surgery in 12 hospitals of Gansu Province were investigated, focusing on education, resident rotation train-ing, teachers' qualification, refresher training, the frequency of intra-hospital technical exchange, and scale of hospital employed. SPSS 18.0 statistical software was applied to analyze the data. t test was used in com-parison between groups, and multiple groups were compared by using single factor analysis of variance. Results The surgeon growth time was (9.84±1.51) years averagely. In the process of growing up, the growth time of the general surgeons who experienced hospital resident rotated training, refresher training, intra-hos-pital technical exchange was significantly shorter than that of no-related-experienced surgeons. The higher the education, the higher the quality of the teachers and the higher the level of medical institutions, the shorter the doctor's growth time. Conclusion In the same medical institutions, the resident rotated training, the teacher's qualification, higher hospital training, and the frequency of intra-hospital technical exchange have the positive function to the surgeon's general growth, so in making young doctor training plan we should consider the value of the above-mentioned factors.