OBJECTIVE:To compare clinical efficacy and safety of intravenous dripping of methotrexate and uterine arterial perfusion embolization combined with complete curettage of uterine cavity (CCUC) in the treatment of cesarean scar pregnancy (CSP).METHODS:A total of 90 CSP patients were randomly divided into group A and B,with 45 cases in each group.Group A was given Methotrexate (MTX) injection 50 mg/m2 intravenously before CCUC.Group B received Seldinger catheterization in supine position before CCUC,and was given sequential infusion of MTX injection 50 mg/m2 and gelatin sponge particles into the uterine artery;the catheter was removed after satisfactory embolization by imaging examination.The levels of β-HCG of 2 groups were reexamined every 24 h,and CCUC was performed when serum β-HCG level was below 1 000 mU/mL.Perioperative bleeding volume,postoperative bleeding volume,the time of blood β-HCG returning to normal,the time of menstruation returning to normal,hospitalization time as well as the lesion diameters,the levels of blood β-HCG,the occurrence of compliance and ADR before and after treatment were compared between 2 groups.RESULTS:The intraoperative bleeding amount and postoperative bleeding amount of group B were significantly lower than those of group A,while the time of blood β-HCG returning to normal,the time of menstruation returning to normal and hospitalization time were significantly shorter than group A,and the incidence of total compliance was significantly lower than group A,with statistical significance (P＜0.05).Before medication,there was no statistical significance in lesion diameters between 2 groups (P＞0.05).Before CCUA,the lesion diameters of 2 groups were significantly smaller than before medication,and the group B was significantly smaller than group A,with statistical significance (P＜0.05).Before medication,there was no statistical significance in blood β-HCG levels between 2 groups (P＞0.05).Before and after CCUC,blood ββHCG levels of 2 groups were significantly lower than before medication,and the group B was significantly lower than group A,with statistical significance (P＜0.05).There was no statistical significance in the incidence of ADR between 2 groups (P＞0.05).CONCLUSIONS:Compared with methotrexate by intravenous drip,methotrexat by uterine artery embolization combined with CCUC for CSP can effectively reduce intraoperative bleeding amount,promote the decrease of blood β-HCG and menstrual recovery,and contribute to the reduction of complication risk with good safety.

OBJECTIVE To evaluate the possibility that CdCl2 induces autophagy and apoptosis in HEK293 cells,and the role of extracellular regulated protein kinases (ERK1/2) and AKT proteins in autophagy. METHODS Green fluorescence protein(GFP)-light chain 3B(LC3B)expression plasmid was transfected into HEK293 cells. After 24 h,HEK293 cells were induced with CdCl2 2,4,8 and 10μmol·L-1 for 12 h. The expression of GFP-LC3B was detected by fluorescent microscopy. HEK293 cells were induced with CdCl2 2,4,8 and 10μmol · L-1 without transfection of GFP-LC3B for 12 h while autophagic vacuoles were observed by transmission electron microscopy. The expression of LC3B-Ⅱ/Ⅰproteins and the phosphorylation levels of ERK1/2 and AKT were analyzed by Western blotting. Apoptosis was detected by flow cytometry microscopy. HEK293 cells were treated with 3-MA 20μmol · L-1+CdCl2 10 μmol · L-1 for 12 h before cleaved caspase 3 protein was detected by Western blotting. RESULTS When HEK293 cells were exposed to CdCl2(≤10μmol · L-1)for 12 h,cytoplasmic GFP-LC3B punctuates were observed under the fluorescence microscope,and autophagic vacuoles were observed under an electron microscope. The expression of LC3B-Ⅱ/Ⅰ,p-ERK1/2 and p-AKT proteins was significantly increased in CdCl2-induced cells(P<0.05,P<0.01). Moreover,apoptosis was observed. The addition of 3-MA 20μmol · L-1+CdCl2 10μmol · L-1 enhanced apoptosis. Cleaved capase 3 protein expression was significantly increased(P<0.01). CONCLUSION CdCl2(≤10μmol·L-1)can induce autophagy in HEK293 cells. ERK1/2 and AKT proteins might be associated with the activation of autophagy that is accompanied by apoptosis,suggesting that autophagy can inhibit apoptosis at certain concentrations of CdCl2.

Objective To investigate the effects of grape seed proanthocyanidin(GSPE) on mitochondrial injury in hippocampus and learning-memory impairment after obstructive sleep apnea hypoxia in rats.Methods Male SD rats(n=80) were randomly divided into control group,model group,low dose of GSPE treatment group and high dose of GSPE treatment group.Rats in control group were exposed in air,the model group were suffered from intermittent hypoxia conditions (50 ml/L,8-hour-intermittent hypoxia everyday,and the duration of experiment 2 and 6 weeks,respectively).Mitochondrion pathology in hippocampal region was observed using electron microscope;malondialdehyde (MDA) contents and superoxide dismutase activity were detected by colorimetry and apoptotic cells was measured by TUNEL method.The cognitive function of rats in each group was assessed with the Morris water maze (MWM).Results After hypoxia,mitochondrion was significantly injured.The MDA contents were increased(79.86 ± 2.52,88.26 ± 2.86) and SOD level decreased (70.67 ± 6.70,64.26 ± 7.86).The number of neural apoptotic cells was significantly enhanced (9.68 ± 0.79,15.9 ± 2.92).MWM test showed that the escaping latency was prolonged and the frequency of crossing the platform was decreased (P ＜ 0.05).Compared with that in the model group,low dose of GSPE decreased MDA contents (76.38 ± 1.96,82.16 ±2.02),increased SOD level(76.20 ± 6.86,70.58 ± 6.86),and decreased apoptotic cells (6.60 ± 0.69,9.54 ±1.36).MWM test showed that the escaping latency was shortened and the frequency of crossing the platform was increased in GSPE treatment groups(P ＜ 0.05).Compared with low dose of GSPE,high dose of GSPE decreased MDA contents increased SOD level and decreased apoptotic cells.MWM test showed that the escaping latency was shortened and the frequency of crossing the platform was increased (P＜ 0.05).Conclusion GSPE can attenuate mitochondrial injury and improve learning-memory function after obstructive sleep apnea hypoxia.

Microglia play a crucial role in inflammation after cerebral ischemia.A large number of studies have shown that microglia are highly plastic cells that can assume different phenotypes and functions in response to specific microenvironmental signals.Microglia can be polarized into the classically activated proinflammatory M1 phenotype or the alternatively activated anti-inflammatory M2 phenotype,and play different roles in ischemic injury.Irnhibiting M1 while stimulating M2 may be a new approach for the treatment of ischemic stroke.

Objective To evaluate the clinical effect of Tanreqing in the treatment of radiation pneumonia. Methods 75 patients with radiation pneumonia were randomly divided into treatment group and control group according to the registration of this study.38 cases in the treatment group treated by Tanreqing,antibiotics and glucocorticoid,while 37 cases in the control group was given antibiotics and glucocorticoid.Then,the therapeutic efficacy was compared.Results From the chest routine scan result and the clinical symptom release,the excellence rate of the treatment group was 68.4%,which of the control group was 43.2%,there was statistically significant difference between the two groups (χ2 =4.823,P =0.028 ).Conclusion Treating radiation pneumonia with Tanreqing has good effect,and it is worthy of clinical application.

Objective To evaluate the role of the angiotensin Ⅱ type 2 receptor (AT2R) in repeated propofol anesthesia-induced neuroapoptosis in the hippocampus of newborn rats.Methods Fiftyfour pathogen-free Sprague-Dawley rats,aged 7 days,weighing 10-15 g,were divided into 3 groups (n=18 each) using a random number table:control group (group C),repeated propofol anesthesia group (group P) and AT2R agouist CGP42112A group (group G).In group C,0.9％ sodium chloride injection 3 ml/kg was intraperitoneally injected,and half of the initial dose 1.5 ml/kg was given every 20 min for 5 times in total,lasting for 3 consecutive days.In group P,propofol 30 mg/kg was intraperitoneally injected,and half of the initial dose 15 mg/kg was given every 20 min for 5 times in total,lasting for 3 consecutive days.In group G,a single bolus of CGP42112A 1 mg/kg was intraperitoneally injected,propofol 30 mg/kg was intraperitoneally injected 5 min later,and half of the initial dose of propofol 15 mg/kg was given every 20 min for 5 times in total,lasting for 3 consecutive days.At 2 h after emergence from anesthesia,6 rats were sacrificed and brains were removed for detection of neuroapoptosis in the hippocampus by TUNEL assay.The apoptosis index was calculated.Another 6 rats were sacrificed,brains were removed and hippocampi were isolated for determination of the expression of activated caspase-3,AT2R and peroxisome proliferator-activated receptor gamma (PPARγ) in hippocampal tissues by Western blot.The other 6 rats were fed until 28 days old,and the cognitive function was then assessed using Morris water maze test.Results Compared with group C,the escape latency was significantly prolonged,the time of staying at the target quadrant was shortened,the frequency of crossing the platform was decreased,the apoptosis index was increased,the expression of activated caspase-3 was up-regulated,and the expression of AT2R and PPARγ was down-regulated in group P (P＜0.05),and no significant change was found in the parameters mentioned above in group G (P＞0.05).Compared with group P,the escape latency was significantly shortened.the time of staying at the target quadrant was prolonged,the frequency of crossing the platform was increased,the apoptosis index was decreased,the expression of activated caspase-3 was down-regulated,and the expression of AT2R and PPARγ was up-regulated in group G (P＜0.05).Conclusion Inhibited activity of AT2R is involved in repeated propofol anesthesia-induced neuroapoptosis in the hippocampus of newborn rats.

Objective To clarify the effects of exercise- and food intake restriction-induced weight reduction on expression of ghrelin in plasma and stomach of obese rats,and to explore the role of ghrelin during weight loss. Methods 100 weaned Sprague-Dawley(SD) rats were randomly divided into control group(fed with standard chow,n= 20) and model group (two-bottle-feeding method,fed with standard chow and high-fat diet simultaneously, n=80). After 20 weeks feeding, Lee' s index of control was used as the reference of diet-induced obesity identification, and then diet-induced obese rats were randomly divided into four groups:obese control group,swimming group,food intake restriction group and swimming+food intake restriction group, eight rats in each group. Rats in swimming group underwent long-term(40 min,6 days/week for 5 weeks)swimming exercise. Calorie in food intake restriction group was restricted 1/3 of normal kcal for 3 weeks,and subsequently restricted 1/3 for 2 weeks. Swimming+food restriction group had the same intervention as swimming and food restriction group. 8 normal diet rats were also chosen as controls. After five weeks of treatments,peripheral fat mass of testis and kidney,ghrelin proteins in plasma and stomach,and ghrelin mRNA in stomach were measured. Results Gastric ghrelin protein and mRNA were significantly lower in obese control group than those in normal control group (P<0.05). However, plasma ghrelin did not decrease markedly in obese control rats(P>0.05). Compared with obese control group,weight and fat mass in all weight loss groups declined notablely(P<0.05);in swimming and swimming+food restriction groups,the expression of ghrelin protein or mRNA in plasma or stomach increased remarkably( P<0.05); in food restriction group, the level of ghrelin mRNA raised significantly (P<0.05), while ghrelin protein in plasma and stomach had not change. Conclusion The level of ghrelin increased in exercise induced weight loss,while showed no significant change in food intake restriction group, suggested that ghrelin might be involved in the process of weight loss induced by exercise.

Objective To investigate the changes in the expression of phosphatidylinositol 3?kinase(PI3?K),mammalian target of rapamycin (mTOR)and Beclin?1 in the hippocampus of normal rats and intermittent hypoxia rats with cerebral ischemia/reperfusion ,so as to explore the role of PI3K/mTOR/autophagy pathway in global cerebral ischemia/reperfusion injury aggravated by intermittent hypoxia. Methods A total of 80 healthy male Wistar rats were randomly divided into sham operation group(SO group,n=20),merely ischemia/reperfusion group(I/R group,n=20),intermittent hypoxia for 7?day ischemia/reperfusion group(IH7+I/R group,n=20),and intermittent hypoxia for 21?day ischemia/reperfusion group(IH21+I/R group,n=20). IH7+I/R group and IH21+I/R group were respectively given intermittent hypoxia for 7 days and 21 days before ischemia/reperfusion. The cerebral ischemia/reperfusion model was established by modified Pulsinelli four?vessel occlusion method. The morpholog?ical changes of nerve cells in hippocampal CA1 region were observed by HE staining and electron microscope. The protein expressions of PI3?K, mTOR and Beclin?1 of nerve cells in hippocampal CA1 region were detected by immunohistochemical staining and RT?PCR. The learning memory capacity of rats were assessed by the Morris water maze test. Results Compared with SO group,I/R group increased the never cells morphology damages,reduced the number of survival neurons,and declined the ability of learning and memory(P<0.05). Immunohistochemistry showed that the number of PI3?K immunoreactive cell,mTOR immunoreactive cell and Beclin?1 immunoreactive cell increased in I/R group compared with S0 group(P<0.05). RT?PCR showed that the expressions of PI3?K,mTOR and Beclin?1 increased in I/R group compared with S0 group(P<0.05). Compared with I/R group,intermittent hypoxia groups increased the never cells morphology damages,decreased the number of survival neu?rons,and declined the ability of learning and memory(P<0.05). Immunohistochemistry showed that the number of PI3?K immunoreactive cell, mTOR immunoreactive cell and Beclin?1 immunoreactive cell increased in IH7+I/R and IH21+I/R groups compared with I/R group(P<0.05). RT?PCR showed that the expressions of PI3?K,mTOR and Beclin?1 increased in IH7+I/R and IH21+I/R groups compared with I/R group(P<0.05),and the changes were more significant in IH21+I/R group(P<0.05). Conclusion Intermittent hypoxia can aggravate neurological injury after ischemia,which is related to PI3K/mTOR/autophagy pathway activation.

Background Penetrating keratoplasty (PKP) has become an effective method of treatment for fungal keratitis in recent years,but the application timing of glucocorticoids after PKP is still unclear.Literature reported that the concentration of tear (1,3)-β-D-glucan in fungal keratitis was significantly higher than that in normal.Objective This study was to investigate the change of tear (1,3)-β-D-glucan before and after PKP in fungal keratitis and to explore the application duration of anti-fungal drugs and application timing of glucocorticoids.Methods This study protocol was approved by ethic committee of Affiliated Hospital of Qingdao University.A serial cases-observational study was performed from August,2011 to December,2012.Twenty eyes of 20 patients with fungal keratitis were collected in Affiliated Hospital of Qingdao University.PKP was performed in affected eyes,and the fellow health eyes served as controls.Tear of 50 μl was obtained in the controls on 1 day before operation and 1 day,7,14,21 and 28 days after operation to detect tear (1,3)-β-D-glucan levels.Results Tear (1,3)-β-D-glucan levels were (14.67±3.84)mg/L,(1 861.66±196.17) mg/L,(927.71±155.82)mg/L,(392.30±71.22)mg/L,(179.60±40.47) mg/L,(40.20± 12.46) mg/L and (15.12± 1.80) mg/L in the control group,preoperative 1 day,postoperative 1 day,7,14,21,28 days,respectively,showing a significant difference among various time points (F=883.45,P=0.00).Tear (1,3)-β3-D-glucan levels were gradually reduced with the lapse of the postoperative time,with significant differences between adjacent timepoints (t' =13.84,t =16.67,t' =11.02,t' =13.97,t' =-8.45,all at P=0.00).Tear (1,3)-β-D-glucan levels in postoperative 28 days came near that of normal control group,without significant difference between them (P =0.64).Fungal keratitis recurred in 2 eyes on the fifth and sixth day after operation,with the tear (1,3)-β-D-glucan levels of 2 350.24 mg/L and 1 992.82 mg/L,respectively.Conclusions The concentration of (1,3)-β-D-glucan in the tears increases in the eyes with fungal keratitis and drops to normal range at 28 days after PKP,indicating that the antifungal eyedrops should be applied until 4 weeks after PKP,and this is an optimal timing of using corticosteroid eyedrops to resist reject reaction.

Objective To observe the effects of different anesthetic solutions on postoperative cognitive function and serum S100β protein levels.Methods A prospective randomized controlled trial was conducted. Ninety patients necessary to perform off-pump coronary artery bypass grafting (op-CABG) in Tianjin Chest Hospital from November 2013 to July 2014 were enrolled. They were divided into three groups by random number table: P1, P2 and P3 groups, 30 cases in each group. The anesthesia was maintained with propofol by target-controlled infusion (TCI) in all the patients in the three groups, and the respective dosages were < 2.0μg/mL, 2.0 - 3.0μg/mL and > 3.0 - 4.0μg/mL. The operation time, anesthesia time, dosages of propofol and the incidence of postoperative cognitive dysfunction (POCD) were compared among the three groups. At the following times: before induction of anesthesia (T0), completion of anesthesia induction (T1), after tracheal intubation (T2), skin incision (T3), 1 hour after operation (T4), 2 hours after operation (T5) and the end of operation (T6), the narcotrend index (NTI) and hemodynamic levels were observed; the serum S100β protein levels were measured at the following times: before induction of anesthesia (Ta), 2 hours after operation (Tb), the end of operation (Tc), postoperative 6 hours (Td) and postoperative 24 hours (Te).Results There were no significant differences in operation times and anesthesia times among three groups (allP > 0.05); dosages of propofol in P2 and P3 groups were obviously higher than those of P1 group (mg: 1 746.3±43.9, 2 332.7±42.8 vs. 968.5±35.6, bothP < 0.05), and the incidences of POCD in P2 and P3 groups were lower than that in P1 group (10.00%, 6.67% vs. 33.33%, bothP < 0.05). With the extension of anesthesia time, the level of NTI was gradually declined in each group, in P3 group, it was occasionally increased at T6, and beginning from time point T1 afterwards, the NTI levels were lower than those of P1 and P2 groups at all the time points (allP < 0.05); the mean arterial pressure (MAP) in the three groups had a tendency of firstly going down and then increasing, and the inflection point being at T2, in P1 group, the elevation of MAP level persisted to T4, and it began to decline at T5, while in P2 and P3 groups, the levels started to decline at T4; the heart rate (HR) in three groups showed a tendency of firstly going up and then declining, and the inflection point being at T3; until T6, in P3 group, MAP and HR were all lower than those of P1 and P2 groups, the differences being statistically significant [MAP (mmHg, 1 mmHg = 0.133 kPa): 74.9±8.3 vs. 85.3±11.2, 84.2±10.1;HR (bpm): 74.1±4.2 vs. 80.9±8.1, 78.7±7.9, allP < 0.05]. The serum S100β protein levels of three groups at Tb began to be obviously higher than those at Ta, and reached the peak points at Tc, then the levels started to decline until Td, and the levels at Te was approximately close to those of Ta, but the serum S100β protein levels in P2 and P3 groups were lower than that in P1 group, the differences being statistically significant (mg/L: 1.05±0.22, 1.04±0.21 vs. 1.33±0.22, bothP < 0.05).Conclusion Application of propofol by TCI 2.0 - 3.0μg/mL for maintenance of anesthesia can achieve the satisfactory depth of anesthesia, and it not only can reduce the effects on hemodynamics, but also can decrease the serum S100β protein level and the incidence of POCD.