Objective To screen the preparation process of 3,4,3″-trihydroxy p-terphenyl nanosuspension. Methods The nanosuspension was prepared in combination with the nanoprecipitation and microfluidization method. Taken the particle size for indicator, we investigated the stirring speed and precipitation temperature in the nanoprecipitation process, the homogeneous stress and cycles in the microfluidic process through single factor experiment. In addition, by factorial design, the variety and dosage of stabilizers are investigated. Results The excellent preparation condition of the nanosuspension are as follows: 0 ℃ for the precipitation temperature, 900 rpm for the stirring speed, 1600 bar for the microfluidization pressure and 12 times for cycles. The ingredient ratio for drug: poloxamer 188: lecithin is 1: 0.8: 0.8. Conclusion Through optimizing the preparation technology, we have successfully prepared nanosuspension with lower size , which will lay a foundation for further study.

Objective To explore the value of energy spectrum CT in the diagnosis of breast cancer.Methods Thirty-two hospitalized patients whose American Colledge of Radiology (ACR) breast imaging reporting and data system (BI-RADS) scores were 4-5 by mammography received non-enhanced spectral CT scans.The spectrum images,spectrum curve,lesion's size,morphology were observed,and also the pectoralis major muscle and axillary lymph node metastasis were evaluated and compared with mammography.Results Thirty-two patients were confirmed by pathology,including 16 cases of invasive duct carcinomas,1 case of medullary carcinoma,15 cases of lobular carcinomas,and 11 cases of the pectoralis major muscle invaded,9 cases of the axillary lymph nodes metastasis.ACR BI-RADS scores 4 were 23 cases,5 were 9 cases.Axillary lymph node metastasis and primary tumor spectrum curves were basically the same.Energy spectrum CT showed the lesion's shape,size,the relationship with the pectoralis major muscle and axillary lymph node metastasis.In 40-70 keV spectrum curve breast cancer displayed a downward trend.There were no significant differences between energy spectrum CT and mammography for the lesion's shape,edge,internal calcification and thickening of adjacent skin (P ＞ 0.05).While energy spectrum CT exhibited obvious advantages in demonstrating the pectoralis major muscle invaded and axillary lymph node metastasis (P ＜ 0.05).Conclusion Energy spectrum CT imaging displays greater clinical value for diagnosing breast cancer,and it can provide multi-parameter image for supporting clinical practice.

Objective To observe the effect of neuromuscular facilitation technique and swallowing training combined with real-time electrical stimulation on dysphagia after stroke. Methods 50 patients with dysphagia were divided into treatment group (n=25) and control group (n=25).The treatment group accepted neuromuscular facilitation technique and VOCASTIM.The control group accepted routine vocal training and low frequency pulse electrical stimulation. They were assessed with the deglutition function classficaition and water drinking test. Results There was significant improvement in the both groups 2 weeks and 4 weeks after treatment (P<0.05), and it improved more in the treatment group than in the control group (P<0.05). Conclusion Neuromuscular facilitation technique and swallowing training combined with real-time electrical stimulation can promote the recovery of function of patients with dysphagia after stroke.

Objective To observe gene different expression of unfolded protein response signaling pathway in human osteoblasts under the excessive fluoride ,and explore the role of endoplasmic reticulum stress in fluorosis .Methods Human osteoblasts were cultured with fluoride ,intervening for 24 h .Cell viability and apoptosis were inspected by MTS assay and flow cytometer respective‐ly .The UPR signaling pathway was examined by real time PCR array ,and protein expressions were detected by Western blot .Re‐sults T he cell survival rates w ere (100 .678 5 ± 2 .830 3 )% ,(105 .393 4 ± 2 .538 4 )% ,(106 .125 7 ± 2 .048 3 )% ,(77 .977 3 ± 2 .544 3)% (P<0 .05) ,(30 .237 7 ± 0 .632 73)% (P<0 .05) treated with sodium fluoride at the concentration 0 ,5 ,10 ,20 ,40 ,80 mg/L respectively .Apoptosis rate inspected by flow cytometer was 4 .8% in 5 mg/L group ,13 .8% in 10 mg/L group ,37 .0% in 20 mg/L group ,58 .9% in 40 mg/L group ,63 .2% in 80 mg/L group (P<0 .05) .Only 1 gene was down regulated and 14 genes were up regulated .Western blot analysis showed BIP ,ATF4 ,CHOP and IRE1 both showed their protein expression gradually up regula‐ted with fluorine dose .XBP1 expression gradually increased in NaF 5-20 mg/L ,and its expression decreased at 40 and 80 mg/L . Conclusion Sodium fluoride can cause osteoblasts endoplasmic reticulum stress pathway through PTEN and IRE1 pathway ,and at high concentrations can cause apoptosis of osteoblast .

BACKGROUND: Microglia play an important role in immune surveillance in their quiescent state, but the role of the activated microglia is under discussion. OBJECTIVE: To analyze the mechanism of activated microglia in acute cerebral infarction. METHODS: Totally 96 male Kunming mice were selected and randomly divided into four groups, including transplantation, placebo, blank control and sham operation groups. Permanent occlusion of the middle cerebral artery was performed using suture method in the mice of the transplantation, placebo and blank control groups, followed by injection of microglia suspension via subclavian vein, medium containing the same volume of microglia, and nothing, respectively, at 12 hours after modeling. In the meanwhile, the same amount of microglia suspension was injected into the mice of the sham operation group. The Zea-longa scale and brain-derived neurotrophic factor expression at 12, 24 and 72 hours after modeling, the volume of cerebral infarction and the number of nerve cells positive for microtubule-associated protein-2 at 72 hours after modeling were detected. RESULTS AND CONCLUSION: The Zea-longa scale score was 0 point in the sham operation group, which was significantly lower than that in the other three groups at each time point after modeling (P < 0.01). The Zea-longa scores in the transplantation group were significantly lower than those in the placebo and blank control groups at 24 and 72 hours after transplantation (P < 0.01). The positive expression rate of brain-derived neurotrophic factor in the transplantation group was significantly higher than that in the other three groups after transplantation (P < 0.01). The sham group showed no infarction, while the size of cerebral infarction in the transplantation group was significantly lower than that in the placebo and blank control groups (P < 0.01), and the microtubule-associated protein-2 positive rate was significantly higher than that in the placebo and blank control groups (P < 0.01). These results manifest that the activated microglia can improve the survival rate of nerve cells, promote the recovery of cerebral nerve function and reduce the size of cerebral infarction.

Objective To observe quantitatively the optic radiation alterations in chronic Leber's hereditary optic neuropathy (LHON) using MR diffusion tensor imaging at 3.0 T.Methods Twenty-five patients with chronic LHON and twenty-eight sex-and age-matched disease-free control subjects wereenrolled from March 2011 to December 2014.The whole brain DTI examination and retinal opticalcoherence tomography were performed in all the subjects.The parameters values of optic radiation includingfractional anisotropy(FA),mean diffusivity(MD),principal eigenvalue(λ//),orthogonal eigenvalue(λ⊥) and average retinal nerve fiber layer (RNFL) thickness and temporal retinal nerve fiber layer(RNFL) thickness were measured.For DTI and OCT parameters,differences between patients and controls and differences right and left of the patient group were evaluated using independent-samples t test and paired t test respectively.Results In LHON patients,the DEC maps showed that the bilateral optic radiation fibers were obviously sparse and slender.The values of FA,MD,λ// and λ⊥ in the right optic radiation were 0.523±0.050,(0.903±0.061) × 10-9 mm2/s,(4.999 ±-0.097) × 10-9 mm2/s and (4.126-± 0.065) × 10-9 mm2/s respectively,and the corresponding values of left optic radiation were 0.537±0.041,(1.057±0.573)× 10-9 mm2/s,(5.052±0.119)×10-9 mm2/s and (4.138±0.072)×1009 mm2/s.Compared with optic radiation in the control group,the bilateral FA was significant reduced,the bilateral λ⊥ value and right MD value were significant increased (t=-6.524,-6.045,6.932,6.454,3.471,P＜0.05).However,there were no significant difference of the bilateral λ〃 and left MD (t=-0.457,1.221,1.833,P＞0.05).There were no significant differences in FA,MD,λ//and λ⊥ between the left and right eyes in LHON patients(P＞0.05).The values of average RNFL thickness and temporal RNFL thickness in right eyes were (59.36± 10.94) and (41.72±9.43) μm respectively,and the corresponding values of left eyes were (60.12±9.81),(44.72±9.43) μm.The average and temporal RNFL thickness were significantly thinned in LHON patients compared with the control group(t=-16.357,-10.398,-17.169,-9.672,P＜0.05).There was no significant difference in average RNFL thickness between the left and right eyes (t=0.959,P＞0.05),temporal RNFL thickness between the left and right eyes was statistically significant (t=2.645,P＜0.05).Conclusion The bilateral optic radiation had significant degeneration and atrophy in chronic LHON.

Background:Accumulating evidence links colorectal cancer (CRC) with the gut microbiota.Fusobacterium nucleatum (F.nucleatum) has been revealed to be involved in the development of CRC, however, the mechanism of F.nucleatum in mediating colorectal tumorigenesis is still poorly understood.Aims:To investigate the effect and potential mechanism of F.nucleatum on CRC.Methods:Wild type C57BL/6 mice and APC(Min/+) mice characterized by multiple intestinal neoplasia were used in this animal study.After administered with F.nucleatum intragastrically and/or 1,2-dimethylhydrazine (DMH, a carcinogen) subcutaneously, the aberrant crypt foci (ACF) and colonic tumor were counted at 8th and 20th week, respectively.Structural alteration of intestinal microbiota and mucosal immune factors were detected in wild type C57BL/6 mice receiving different interventions by using Roche 454 GS FLX pyrosequencing and Bio-Plex ProTM cytokine assay, respectively.Results:In DMH-treated wild type C57BL/6 mice or APC(Min/+) mice, number of ACF and colonic tumor in those administered with F.nucleatum were significantly higher than those without (P<0.05).F.nucleatum colonization significantly altered the lumen microbial structure, with decreased Cyanobacterium and increased Tenericutes and Verrucomicrobia (P all <0.05).Furthermore, F.nucleatum up-regulated expressions of tumor-related immune factors in colonic mucosa, such as IL-21, IL-22, IL-31 and CD40L (P<0.05).Conclusions:F.nucleatum colonization in intestine may prompt colonic tumorigenesis in mice via inducing intestinal dysbiosis and modulating tumor-related immune factors expression.

Objective:To investigate the effect of dexmedetomidine combined with butorphanol on perioperative analgesia in patients subjected to cardiac surgery.Methods:Sixty-three patients who underwent elective cardiac surgery in Weihai Central Hospital from June 2019 to August 2020 were included in this study. They were divided into propofol + sufentanil group ( n = 21), dexmedetomidine + sufentanil group ( n = 23) and dexmedetomidine + butorphanol group ( n = 19) according to different analgesic methods. Postoperative analgesic satisfaction, Visual Analogue Scale score, hemodynamic changes (heart rate, respiratory rate, systolic blood pressure, diastolic blood pressure) and adverse reactions were compared among the three groups. Results:The satisfaction rate of postoperative analgesia in the dexmedetomidine + butorphanol group was 94.7% (18/19), which was significantly higher than 61.9% (13/21) in the propofol + sufentanil group and 60.8% (14/23) in the dexmedetomidine + sufentanil group ( χ2 = 6.16, 6.57, both P < 0.05). At 4, 12, 24 and 48 hours after tracheal extubation, Visual Analogue Scale score in the dexmedetomidine + butorphanol group were significantly lower than that in the propofol + sufentanil group and dexmedetomidine + sufentanil group (both P < 0.05). At the time of tracheal extubation and at 5 minutes after tracheal extubation, heart rate, respiratory rate, systolic blood pressure and diastolic blood pressure in the dexmedetomidine+butorphanol group were significantly lower than those in the propofol + sufentanil group and dexmedetomidine + sufentanil group (both P < 0.05). The incidence of adverse reactions in the dexmedetomidine + butorphanol group was 10.5% (2/19), which was significantly lower than 23.8% (5/21) in the propofol + sufentanil group and 30.43% (7/23) in the dexmedetomidine + sufentanil group [30.4% (7/23), χ2=21.94, P < 0.001]. Conclusion:Dexmedetomidine combined with butorphanol in cardiac surgery can not only stabilize postoperative blood pressure and heart rate, but also lower the degree of pain and is highly safe.

Objective:To study the correlation between insulin-like growth factor-1 (IGF-1) and its receptor IGF-1R expression in ovarian cancer and clinicopathological features, surgical prognosis.Methods:The positive expression rates of IGF-1 and IGF-1R in ovarian cancer, borderline ovarian tumors and benign ovarian tumors were detected by immunohistochemistry. The correlation of IGF-1 and IGF-1R with clinicopathological features, surgical prognosis was analyzed.Results:The positive expression rate of IGF-1 and IGF-1R in ovarian cancer was 65.63%, 70.31%, significantly higher than 22.22%, 16.67% in borderline ovarian tumors, 5.00%, 10.00% in benign ovarian tumors ( χ2/ P=27.548/0.000, 31.335/0.000) . The mRNA and protein expression of IGF-1 and IGF-1R were also significantly higher than borderline ovarian tumors and benign ovarian tumors ( F/P=31.922/0.000, 26.865/0.000, 34.567/0.000, 27.667/0.000) . The positive expression rates of IGF-1 and IGF-1R in ovarian cancer with FIGOIII-IV stage, tissue differentiation G2-G3 stage, CA125>35 U/mL, Ki-67 positive expression were significantly higher than those in ovarian cancer with FIGOI-II stage, tissue differentiation G1 stage, CA125<35 U/mL, Ki-67 negative expression (IGF-1: χ2/ P=8.505/0.004, 4.980/0.026, 7.481/0.006, 10.907/0.001, IGF-1R: χ2/ P=9.785/0.002, 4.950/0.026, 7.211/0.007, 6.471/0.011) . The total survival time of ovarian cancer patients with positive IGF-1 and IGF-1R was shorter than those of patients with negative IGF-1 and IGF-1R. Conclusion:IGF-1 and IGF-1R are highly expressed in ovarian cancer and are associated with the deterioration of pathological features and surgical prognosis.

Objective To observe the characteristics of magnetic resonance angiography of(MRA) ophthalmic artery in patients with diabetic retinopathy (DR).Methods A total of 36 eyes of DR patients (DR group) diagnosed by clinical examination were included in the study.Among them,there were 42 eyes in 21 males and 15 eyes in 15 females.The average age was 55.2 years old.The average duration of diabetes was 7.56 years.All eyes were examined by MRA and fluorescein fundus angiography (FFA) in the ophthalmic artery.At the same time,24 eyes of 12 patients were examined by computed tomography angiography (CTA).Twenty-two healthy volunteers with age and gender matching were selected as the control group.Among them,there were 13 males and 9 females.All patients underwent MRA examination of the ophthalmic artery;at the same time,5 eyes of 5 eyes were examined by CTA.MRA and CTA were classified into three grades according to the development condition and shape change of the ophthalmic artery.0 grade:no abnormality;grade Ⅰ:mild lesion;grade Ⅱ:obvious lesion.According to the results of FFA examination,it was divided into no obvious disease stage,background stage,proliferative stage,proliferative stage.The morphological features of the MRA of the ophthalmic artery in the DR group and the control group were compared.The relationship between the MRA grading of the ophthalmic artery and the FFA staging was observed in the DR group.The consistency analysis between the MRA and CTA grades of the ophthalmic artery in the DR group was performed by Kappa test;the relationship between the MRA grade and the FFA staging of the ophthalmic artery was analyzed by Spearson correlation analysis of the same data with two-way ordered attributes.Results In 44 eyes of the control group,the MRA in grade 0 and Ⅰ of the ophthalmic artery were 41 and 3 eyes,respectively;all eyes of the CTA examination of the ophthalmic artery were grade 0.In 72 eyes of the DR group,the MRA in grade 0,Ⅰ,and Ⅱ of the ophthalmic artery were 28,28,and 16 eyes,respectively.Among the 24 eyes examined by CTA,there were 13,6,and 5 eyes in grade 0,Ⅰ,and Ⅱ,respectively.In the DR group,the classification of MRA and CTA of the ophthalmic artery was highly consistent (Kappa value =0.86).There were significant differences in the number of eyes with different grades of MRA in the DR group and the control group (Z=-5.74,P=0.000).In 72 eyes of the DR group,there were 8,12,22,and 30 eyes in no obvious disease stage,background stage,proliferative stage,and proliferative stage,respectively.Correlation analysis showed that there was a significant correlation between MRA grading and FFA staging in the DR group (r=0.405,P=0.000).Conclusions MRA can show the changes of ophthalmic artery morphology and reflect DR staging to a certain extent.It has a high consistency with FFA vascular changes.