Objective:To investigate the efficacy and safety of tirofiban combined with dual antiplatelet therapy for progressive stroke, and obtain the effective time and speed of intravenous tirofiban.Methods:The patients with progressive stroke from June to December 2018 in the Second Hospital of Liaocheng Affiliated to Shandong First Medical University were divided into 2 groups: 28 patients were treated with dual antiplatelet (dual antiplatelet group) and 22 patients were treated with tirofiban combined with dual antiplatelet (tirofiban group). The demographic characteristics, risk factors of cerebral infarction, new infarct location and possible pathogenesis were recorded. The beginning of tirofiban, National Institutes of Health stroke scale (NIHSS) score at different time points, complications, and intravenous infusion effective time, maintenance dose and speed were recorded. NIHSS score was recorded for 14 d and modified Rankin scale (mRS) score was recorded for 90 d after discharge.Results:After 14 d of continuous treatment in the dual antiplatelet group, the NIHSS score decreased (2.92±1.13) scores. One case had gastrointestinal hemorrhage, and there were no intracranial hemorrhage complications. After 14 days of continuous treatment in the tirofiban group, the NIHSS score decreased (3.46±1.71) scored. One case had skin and mucosa hemorrhage, and there were no intracranial hemorrhage complications. In tirofiban group, the effective time of intravenous infusion was 42.2 to 135.7 (86.6 ± 42.3) h, and the infusion speed was 0.15 to 0.45 (0.31 ± 0.12) mg/h. Compared with the dual antiplatelet group, the NIHSS score and 90-day mRS score of tirofiban group decreased significantly: (3.36 ± 1.71) scores vs. (4.75 ± 2.30) scores and (2.93 ± 1.04) scores vs. (3.52 ± 1.83) scores, and there were statistical differences ( P<0.05). Conclusions:Intravenous tirofiban combined with dual antiplatelet therapy for progressive stroke may be a relatively effective method.

OBJECTIVE: To explore the status and its influencing factors of anxiety symptoms in patients with occupational noise-induced deafness(ONID). METHODS: A total of 220 ONID patients were selected as the ONID group,and 200 healthy participants without noise exposure were selected as the control group by judge sampling method.The two groups were investigated by the Self-Rating Anxiety Scale, Self-Rating Depression Scale and Pittsburgh Sleep Quality Index. The Tinnitus Handicap Inventory was used to evaluate the disability levels of tinnitus, and pure-tone audiometry was used to assess the degree of tinnitus and hearing impairment in the ONID group. RESULTS: The incidence of anxiety, depression, and sleep disorder were higher in the ONID group than that in the control group(52.7% vs 9.0%, 55.0% vs 15.0%, 52.3% vs 7.0%, P<0.05). In ONID with anxiety subgroup, the duration of disease was longer(1.0 vs 2.0 years, P<0.01), incidences of tinnitus, depression and sleep disorder were higher than those in ONID without anxiety subgroup(92.3% vs 100.0%, 18.3% vs 87.9%, 19.2% vs 81.9%, P<0.01). The result of multivariate logistic regression analysis showed that the longer the duration of disease and the more severe of the tinnitus, the higher the risk of anxiety symptoms in patients with ONID [the odds ratio(OR) and its 95% confidence interval(CI) were 1.35(1.10-1.65) and 2.94(1.56-5.54) respectively, P<0.01]. The risk of anxiety in patients with sleep disorders was higher than those without sleep disorders [OR(95%CI) was 12.78(5.90-27.64), P<0.01]. CONCLUSION: The ONID patients are more likely to have anxiety. The duration of disease, severity of tinnitus and sleep disorders are the risk factors causing anxiety in ONID patients.

Although high-efficiency targeted delivery is investigated for years, the efficiency of tumor targeting seems still a hard core to smash. To overcome this problem, we design a three-step delivery strategy based on streptavidin-biotin interaction with the help of c(RGDfK), magnetic fields and lasers. The ultrasmall superparamagnetic iron oxide nanoparticles (USIONPs) modified with c(RGDfK) and biotin are delivered at step 1, followed by streptavidin and the doxorubicin (Dox) loaded nanosystems conjugated with biotin at steps 2 and 3, respectively. The delivery systems were proved to be efficient on A549 cells. The co-localization of signal for each step revealed the targeting mechanism. The external magnetic field could further amplify the endocytosis of USPIONs based on c(RGDfK), and magnify the uptake distinctions among different test groups. Based on photoacoustic imaging, laser-heating treatment could enhance the permeability of tumor venous blood vessels and change the insufficient blood flow in cancer. Then, it was noticed that only three-step delivery with laser-heating and magnetic fields realized the highest tumor distribution of nanosystem. Finally, the magnetism/laser-auxiliary cascaded delivery exhibited the best antitumor efficacy. Generally, this study demonstrated the necessity of combining physical, biological and chemical means of targeting.

Objective To compare the effects of bone transport versus induced membrane technique for large segmental tibial defects.Methods The clinical data were analyzed retrospectively of 89 patients with large segmental tibial defect who had been treated at Department of Orthopaedics,Wuxi No.9 People's Hospital from June 2005 to February 2017 using bone transport or induced membrane technique.They were 58males and 31 females,aged from 13 to 74 years (average,38.0 years).The bone transport group had 59cases and the induced membrane technique group 30 cases.The 2 groups were compared in terms of preoperative general data and postoperative bone nonunion,bone healing time,complications and functional recovery of the adjacent joint.Results There were no statistically significant differences between the 2groups in terms of age,gender,cause or type of defects,associated injury,course of disease,functionary scores of the adjacent joint or number of operations,showing compatibility between the 2 groups (P ＞ 0.05).All the patients were followed up for 12 to 48 months (average,20 months).The bone transport group had significandy longer clinical healing time (14.7 ± 5.4 months) and significantly higher incidences of major complications (50.8％),minor complications (57.6％) and overall complications (83.1％) than the induced membrane technique group (11.2 ± 2.8 months,16.7％,26.7％ and 30.0％,respectively) (P ＜ O.05),but significantly lower functionary scores of the adjacent joint (86.4 ± 5.0 points) than the induced membrane technique group (88.8 ± 4.9 points) (P ＜ 0.05).Conclusions Both bone transport and induced membrane technique are effective repairs for large segmental tibial defects.However,induced membrane technique may be superior to bone transport in terms of bone healing,complications and functional recovery.

Objective: To compare the efficacy of intra-articular injection of autologous platelet-rich plasma (PRP) with that of sodium hyaluronate for patients with knee osteoarthritis (KOA). Methods: Fifty KOA patients were randomly divided into a PRP group (n=25) and a sodium hyaluronate group (n=25). Those in the PRP group were injected intra-articularly with 5 ml of autologous PRP every 2 weeks for 6 consecutive weeks, while the sodium hyaluronate group was given intra-articular injections of 2 ml of sodium hyaluronate once a week for 6 weeks. Both groups performed isokinetic strength training three times a week for 6 weeks. Before as well as 6 weeks, 3 months, 6 months and 12 months after the treatment, both groups were followed and evaluated using the Western Ontario and McMaster University osteoarthritis index (WOMAC). A Biodex System 4 isometric muscle strength testing system was used to evaluate the knees′ peak torque (PT) in flexion and extension, total power (TW), and average power (AP). Results: Before the treatment there were no significant differences in pain, stiffness or average WOMAC score between the two groups. Afterward significant improvement was observed in the pain, stiffness and WOMAC scores of both groups. Compared with the sodium hyaluronate group, significantly greater decreases in the average WOMAC pain score were observed in the PRP group after the different intervals. That was also true of the average stiffness scores and the overall average WOMAC scores after 6 and 12 months. The flexor and extensor PT, TW and AP at the angular velocities of 60°/s and 90°/s also improved significantly in both groups after 6 weeks and 12 months, with the improvement of the PRP group significantly greater than that in the control group at the same time points. Conclusion Intra-articular injection of either autologous PRP or sodium hyaluronate can effectively alleviate the clinical symptoms of KOA when combined with isokinetic strength training. However, PRP is the more effective. Its use is worthy of clinical application and promotion.

Background Corneal collagen cross-linking (CXL) shows good clinical effects for keratoconus,and de-epithelized CXL appears to be benefit to the distribution and absorption of riboflavin in cornea stroma.However,de-epithelization of CXL will increase the infective risk and corneal healing time.It is very important to understand and control the affecting factors of corneal repair after de-epithelization of CXL.Objective This study was to evaluate the characteristics of corneal epithelial repair and analyze the relevant factors affecting corneal healing time after de-epithelized CXL.Methods A series-cases observational study was performed.De-epithelized CXL was performed on 77 eyes of 68 keratoconus patients in Shandong Eye Hospital from September 2013 to September 2015 under the approval of Ethic Committee of this hospital and informed consent of each patient.The age,corneal curvature,corneal thickness,breakup time of tear film (BUT),corneal front astigmatism (Astig) and epithelial healing time of the patients were recorded after surgery.The correlations between corneal epithelium healing time and above-mentioned factors were analyzed.Results De-epithelized CXL was smoothly finished in all the eyes.The corneal epithelium healing time was 2-12 days after surgery,with the average healing time 5 (4,6) days.The mean age,thickness at corneal thinnest point,minimal cornea curvature (Kf),maximal corneal curvature (Ks),corneal average curvature (Km) and Astig was 22.00 (18.00,25.00) years,436 (412,470) μm,47.40 (44.70,50.45) D,52.10 (49.00,54.55) D,50.00 (47.15,53.15) D and-3.30 (-5.45,1.70) D,respectively.Spearman rank correlation analysis showed significant negative correlations between corneal epithelium healing time and BUT or the thickness at corneal thinnest point (BUT:rs =-0.334,P =0.003;corneal thickness:rs =-0.417,P =0.000),and thesignificant positive correlations were found between corneal epithelium healing time and Km,Kf and Ks (Km:rs =0.449,P =0.000;Kf:rs =0.300,P =0.008;Ks:rs =0.432,P =0.000).There were no considerable correlarions between corneal epithelium healing time and age or Astig (age:rs =0.023,P =0.845;Astig:rs =-0.190,P =0.098).Multiple linear regression analysis were carried out to study the dependent variable and independent factors.Because of the multiple co-linearity between variables,this paper corrects the model by using ridge regression.There is significant negative correlation between BUT,corneal thickness and corneal healing time,respectively (both at P＜0.05),corneal curvature Km and Kf is positively correlated with corneal healing time (both at P ＜ 0.05).Conclusions The corneal thickness,Kf,Km,as well as BUT are influencing factors of epithelial healing after CXL.

Objective To observe curative effect of Ningdong granules on tourette syndrome (TS) concomitant with sleep disorder in children.Methods Eighty-three cases were diagnosed by diagnosis and statistics of mental-disorder (DSMIV) TS criterion and diagnostic standard of traditional Chinese medicine,and then were divided into 3 groups:tiapride hydrochloride group (n =25),Ningdong granules group (n =30) and tiapride hydrochloride plus Ningdong granules group (n =28).Yale global tic severity scale (YGTSS) and Athens insomnia scale (Athens) were used for rating the clinical efficacy before and after treatment.The enrolled children were treated for a period of three months.Results The therapeutic effective rate of TS in tiapride hydrochloride group,Ningdong granules group and tiapride hydrochloride plus Ningdong granules group was 92.0％,90.0％ and 96.4％,respectively.The therapeutic effective rate of sleep disorder was 84.0％,93.3％ and 96.4％,respectively.Mter treatment,YGTSS and Athens scores were significantly changed in all three groups (P ＜ 0.05).Athens score was significantly different between tiapride hydrochloride plus Ningdong granules group and tiapride hydrochloride group (P ＜ 0.05).The total number of adverse reactions was 16,1 and 8,with significant difference (P ＜ 0.01).Conclusion Curative effect of Ningdong granules is similar to that of tiapride hydrochloride on treating TS,but Ningdong granules is more effective than tiapride hydrochloride on treating sleep disorder with less adverse reactions.Combination therapy of Ningdong granules with tiapride hydrochloride is the better choice for treating TS with sleep disorder,and it can also reduce the incidence of adverse reactions of tiapride hydrochloride.

Objective To study the pharmacokinetic status of Cyclophosphamide (CYC) in children with lupus nephritis (LN),as well as the relationship between the pharmacokinetic results and clinical indicators,adverse reactions,curative effect evaluation.Methods Thirty patients hospitalized at Tianjin Children's Hospital from January 2014 to December 2016 were treated with glucocorticoid (GC) combined with CYC.Blood samples were collected in 6 point-in-time after intravenous CYC,a high performance liquid chromatography (HPLC) method was used to detect the blood drug concentration,and the pharmacokinetic results were calculated.All patients were followed up for 24 weeks,and the levels of serum albumin (ALB),24 hours urinary protein,serum creatinine (Scr),complement 3 (C3),therapeutic effect and systemic lupus erythematosus disease activity index scores were evaluated at the same time.Results Pharmacokinetic curve showed the second chamber model,the area under the curve (AUC) of time-effect relationship was (143.55 ±42.43) g/(L · h),peak concentration (Cmax) was (20.02 ± 3.55) g/L,and half-time period (T1/2) was(4.21 ± 0.96) h.Age and gender had no influence on AUC,Cmax and T1/2,and statistically significant correlation was found between serum ALB and T1/2,which was positively correlated (r =0.517,P ＜ 0.05).After 16 weeks of treatment,7 patients were partially responsive,22 cases had a complete remission,and the invalid case was only one.Followed up for 24 weeks,6 patients were partially responsive,24 cases had a complete remission.After 16 weeks of treatment,there were statistical differences in AUC among patients with complete response,partial response or no remission.And after 24 weeks,the patients between complete remission and partial remission had no statistically significant difference in the AUC.After 16 weeks and 24 weeks,T1/2 and Cmax had no statistical differences among those groups of patients.Adverse reactions included leukopenia (3 cases,10.00％),gastrointestinal symptoms (4 cases,13.33％) and respiratory tract infection (6 cases,20.00％).There was no statistical relationship between pharmacokinetic parameters and the occurrence of adverse reactions.Single factor analysis showed that there was a statistical significance between ALB,urine protein quantity and treatment effect,but multi-factor analysis showed that the relation between factors and therapeutic effect had no statistical significance.Conclusions HPLC method can be used for the detection of cyclophosphamide blood drug concentration.The cyclophosphamide pharmacokinetic status of children and adult is similar.ALB and T1/2 show a linear positive correlation.Single factor analysis shows a correlation between ALB and treatment effect.Therefore,the increasing level of plasma propagated before treatment can improve therapeutic effect possibly.Cyclophosphamide pharmacokinetic status has nothing to do with the occurrence of adverse drug reactions in the study.

Objective To investigate the difference of CCAAT/enhancer-binding protein α (C/EBP-α) gene induced apoptosis between hepatocytes and hepatic stellate cells (HSC) in mice with liver fibrosis.Methods Sixty BALB/c mice were evenly divided into normal group,model group,treatment group,blank control group and negative control group,12 mice in each group.Except the mice of normal control group,the mice of other groups were treated with intraperitoneal injection of CCl4 to establish liver fibrosis mice model.Mice of treatment group,blank control group and negative control group were administrated with C/EBP-α carried adenovirus (Ad-C/EBP-α),phosphate buffered solution and empty vector of adenovirus (Ad-EGFP) respectively through tail vein for the first week.The expression of C/EBP-α and α-smooth muscle actin (α-SMA) was detected by immunohistochemistry method.Sinusoidal endothelial structure of peri-portal regions and far from portal regions was observed by transmission electron microscope (TEM).Terminal dexynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) was applied to detect apoptosis of cells in liver tissue.The degree of liver fibrosis in mice was determined with sirius red staining and hydroxyproline content measurement.Single factor variance analysis was performed for comparison among multiple groups,and t test was used for comparison between two groups.Results C/EBP-α was expressed in nucleus of hepatocyte in normal control group mice.The expression decreased in model group,blank control group and negative control group.However,the expression of C/EBP-α of treatment group increased,and mainly expressed in cells located in perisinusoidal and perivascular.Hepatic sinusoids was distorted,blood vessel wall thickened.Hepatocyte degeneration and lots of lipid droplets was found in model group,blank control group and negative control group.The thicken degree of endothelial layer of blood vessel of treatment group was lower than that of model group.The percentage of sirius red positive cells of normal group,model group,treatment group,blank control group and negative control group was (0.10±0.03)％,(5.81±0.32)％,(2.32±0.45)％,(6.34± 0.81)％ and (6.10± 0.92)％,respectively; content of hydroxyproline was (0.07±0.00) μg/mg,(0.69 ± 0.10) μg/mg,(0.19±0.06) μg/mg,(0.56±0.03) μg/mg and (0.64±0.08) μg/mg,respectively; the percentage of α-SMA positive cells was (0.50 ±0.03)％,(5.30 ± 0.52)％,(2.15 ± 0.29)％,(5.53 ± 0.43) ％ and (5.42 ± 0.25) ％,respectively; the number of TUNEL positive cells was (0.25 ± 0.08),(0.15±0.02),(7.10±1.53),(0.13±0.03) and (0.18±0.07),respectively.The differences between the groups were statistically significant (F=113.74,148.29,292.43 and 140.25,all P＜0.05).The difference between normal group and model group,between model group and treatment group,between treatment group and blank control group,between treatment group and negative control group were statistically significant (tarirus positive cell =-52.54,-16.20,-10.60 and-7.99,thydroxyproline content =-168.00,11.53,11.07 and 12.54,ta SMA pusitive cells-24.77,-13.82,15.94 and 18.37,tTUNEL positive cells =3.26,-11.91,-11.95 and-11.88,all P＜ 0.05),there was no statistically significant difference between model group and blank control group,between model group and negative control group (both P＞0.05).TUNEL positive cells mainly located in perisinusoidal and perivascular of liver in mice,which was consistent with the distribution of α-SMA-positive cells.Conclusion C/EBP-α could effectively relieve CCl4 induced liver fibrosis in mice mainly through inducing HSC apoptosis,however no apoptosis effect on hepatocytes.

Objective To evaluate the effectiveness of differentiation acupoint massage on the level of blood pressure control and self-efficacy in the elderly with hypertension with yin-deficiency and yangexcess under the model of empowerment education.Methods 80 elderly with hypertension with yin-deficiency and yang-excess were randomly divided into the intervention group and the control group with 40 patients in each group.Both of them received health education of differentiation acupoint massage consisted of 4 weekly sessions.The intervention group received it under the model of empowerment education whilst the other under the model of the general health education.After 4 weeks of sessions,all patients were followed up for 3 months.The blood pressure value was measured before the sessions and 4 weeks and 3 months after the sessions.The scores of self-efficacy was collected before and 3 months later.Results There were significant differences in the blood pressure,self-efficacy between the two groups after the intervention.Conclusions Differentiation acupoint massage under the model of empowerment education can significantly improve patients'self-efficacy and decrease the level of the blood pressure.