OBJECTIVE To investigate the effects of the peroxisome proliferator-activated receptors δ （PPARδ） agonist GW501516 on the injury of pulmonary artery endothelial cells （PAECs） induced by hypoxia and its mechanism. METHODS The cytotoxic effects of GW501516 were observed by detecting the relative survival rate of PAECs； the protein expression of PPARδ was determined by Western blot assay. The cellular model of PAECs injury was established under hypoxic conditions； using antioxidant N-acetylcysteine （NAC） as positive control， the effects of GW501516 on cell injury and reactive oxygen species （ROS） production were investigated by detecting cell apoptotic rate， cell viability， lactate dehydrogenase （LDH） activity and ROS levels. Using nuclear factor erythroid 2-related factor 2（Nrf2） activator dimethyl fumarate （DMF） as positive control， PAECs were incubated with GW501516 and/or Nrf2 inhibitor ML385 under hypoxic conditions； the mechanism of GW501516 on PAECs injury induced by hypoxia was investigated by detecting cell injury （cell apoptosis， cell viability， LDH activity）， the levels of superoxide dismutase （SOD）， glutathione peroxidase （GPx）， catalase （CAT）， malondialdehyde （MDA） and ROS， the expressions of Nrf2， heme oxygenase-1 （HO-1） and cleaved-caspase-3 （C-caspase-3） protein. RESULTS The results demonstrated that hypoxia inhibited the protein expression of PPARδ （P＜0.05）， while GW501516 promoted the protein expression of PPARδ in hypoxia- exposed PAECs without obvious cytotoxic effects. GW501516 inhibited the apoptosis of PAECs， improved cell viability， and reduced LDH activity and ROS levels. GW501516 could up-regulate the protein expression of HO-1 in PAECs and the levels of SOD， GPx and CAT， while down-regulated the levels of MDA and ROS by activating the Nrf2 pathway （P＜0.05）； but Nrf2 inhibitor ML385 could reverse the above effects of GW501516 （P＜0.05）. GW501516 exerted similar effects to Nrf2 activator DMF in down-regulating the expression of C-caspase-3 and inhibiting the injury of PAECs under conditions of hypoxia （P＜0.05）. Moreover， Nrf2 inhibitor ML385 reversed the 163.com inhibition effects of GW501516 on PAECs injury （P＜0.05）. CONCLUSIONS GW501516 can relieve the hypoxia-induced injury of PAECs via the inhibition of oxidative stress， the mechanism of which may be associated with activating Nrf2.

Objective:To know the current situation of kinesiophobia in patients after cardiac surgery under cardiopulmonary bypass, and to clarify its influencing factors, so as to provide reference for developing intervention strategies to improve kinesiophobia level.Methods:This was a cross-sectional study. From February 2022 to September 2022, the patients after cardiac valve surgery under cardiopulmonary bypass in the Second Affiliated Hospital Zhejiang University School of Medicine were investigated by convenience sampling methods. The survey was conducted using the General Information Questionnaire, The Tampa Scale for Kinesiophobia Heart, Exercise Self-Efficacy Scale, Pain Catastrophizing Scale, and Adaptation, Partnership, Growth, Affection and Resolve(APGAR) as research tools, and the influencing factors were analyzed using univariate and binary Logistic regression analysis.Results:A total of 219 patients were included, of which 97 patients (44.3%) had kinesiophobia. The results of binary Logistic regression analysis showed that monthly family income level, first time out of bed after operation, fear of falling, the family APGAR, and pain catastrophizing were significant influencing factors of kinesiophobia in patients after heart valve surgery under cardiopulmonary bypass (all P<0.05). Conclusions:The prevalence of kinesiophobia is high among patients after heart valve surgery under cardiopulmonary bypass. Clinicians should pay attention to patients with low monthly family income level, late first time out of bed after surgery, and fear of falling, as well as strengthen communication with patients and families, focus on the management of acute postoperative pain. In order to reduce or avoid the occurrence of kinesiophobia and enable patients to benefit from early ambulation.

Objective:To explore the feasibility of the clinical implementation of intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) plans with 6MV photon on two Elekta Linacs (Versa HD and Synergy) after beam matching.Methods:The images of 12 patients with nasopharyngeal carcinoma, central lung cancer and prostate cancer were randomly selected, and the IMRT and VMAT plans were designed. Two different dose tools of ionization chamber and three-dimensional detector ArcCheck were used to verify the individualized radiation treatment of 6MV photon beams on two Linacs and compare the differences.Results:The deviations between the doses of two Linacs (Versa HD and Synergy) measured by the ion chamber and treatment planning system were (0.32±1.32)% and (0.54±1.29)%. The differences of all plans were within the range of ±3%, and the deviations of the point dose between two Linacs were within the range of ±2% with no statistical significance (both P>0.05). The γ analysis of verification using ArcCheck showed that the passing rates of all plans under the 2mm/3% and 3mm/3% with 10% threshold conditions were over 95%, respectively. The average differences between two Linacs were 0.19%(2mm/3%) and 0.09%(3mm/3%). Conclusions:The results of performing IMRT/VMAT plans on two Linacs meet the clinical requirements and the differences between two Linacs are small. Hence, the same plans can be implemented interchangeably on different Linacs.

Objective To study the effect of intracerebroventricular injection of leptin on proopiomelanocortin(POMC) and neuropeptide Agouti related protein (AGRP) and fasting blood glucose (FBG) in rats with type 2 diabetes mellitus (T2DM).Methods Eighty male 8-week-age SD rats with T2DM were selected and divided into two groups:intracerebroventricular injection of leptin group(n=40)and intracerebroventricular injection of vehicle control group(n =40).Intracerebroventricular injection of 5 μL/kg(fasting leptin level 15 ng/mL) leptin was performed in the leptin injection group,and the control group was injected with same amount of vehicle instead.After 48 h,the FBG level was determined,and the levels of POMC and AGRP were detected by the titer method.Results The level of FBG in the leptin injection group was significantly lower than that in the control group(P＜ 0.05),the expression of serum POMC in the leptin injection group was significantly higher than that in control group(P＜0.05),The expression of AGRP in the leptin injection group was significantly decreased than control group(P＜0.05).Conclusion intracerebroventricular injection of leptin can significantly reduce the FBG level in rats with T2DM,increases POMC expression and decreases AGRP associated protein expression.

Objective To assess the features of transcranial sonography (TCS) in Parkinson disease (PD) and Alzheimer disease (AD).Methods Totally 38 PD patients (PD group),28 AD patients (AD group) and 26 controls (control group)underwent TCS.The echogenicity of the substantia nigra,widths of third ventricle and parameters of middle cerebral artery among the three groups were analyzed.Results The ratio of hyperechogenicity of substantia nigra in PD group (31/38,81.58％) were higher than those in AD group (8/28,28.57％) and control group (3/26,11.54％;x2 =18.74,30.41,both P＜0.001),and there was no significant difference in hyperechogenicity of substantia nigra between AD group and control group (x2 =2.41,P=0.120).The widths of third ventricle in AD group ([0.82±0.14]cm) were wider than those in PD group ([0.63±±0.16]cm) and control group ([0.56±0.16]cm,both P＜0.001),and there was no significant difference in widths of third ventricle between PD group and control group (P=0.098).The mean velocities in bilateral middle cerebral artery in AD group were lower than that of in PD group and in control group (all P＜0.05).The pulsatility index in right middle cerebral artery in AD group were greater than that in PD group and control group (both P＜0.05).Conclusion According to the changes of echogenicity of substantia nigra,widths of third ventricle and parameters of middle cerebral artery,TCS may provide some useful information for diagnosis of PD and AD.

Objective To evaluate the clinical effect of TAPAS intravascular closed catheter-directed thrombolysis combined with endovascular intervention treatment for Cockett syndrome complicated with deep venous thrombous of lower limbs. Methods The clinical data of 31 patients of Cockett syndrome complicated with deep venous thrombosis of lower limbs were retrospectively analyzed, and the patients were treated with TAPAS intravascular closed catheter-directed thrombolysis combined with endovascular intervention.Results Thirty patients were placed self-expandable stent,and 1 patient was treated by balloon dilation.The pain disappeared and the swelling decreased postoperatively.Twenty-two cases was cured (70.97%, 22/31), 7 cases showed excellence (22.58%, 7/31), and 2 cases showed effective (6.45%, 2/31), and there were no invalid patients. There was no pulmonary embolism and bleeding event during treatment. Conclusions The TAPAS intravascular closed catheter-directed thrombolysis combined with endovascular intervention treatment for Cockett syndrome complicated with deep venous thrombous of lower limbs is an effective and safe technique with satisfactory short term result.However,the long term clinical effect need to be further researched.

Objective To investigate the effects of attentional bias training on mood and disease uncertainty in anxious patients with coronary artery intervention treatment during transition period. Methods A total of 82 anxious patients with coronary artery intervention treatment during transition period were assigned into control group (28 cases), escape-negative-training group(27 cases) and positive-direction-training group (27 cases) by random digits table method. Patients in control group only received routine psychological counseling, while patients in escape-negative-training group and positive-direction-training group also received spot-type attentional bias training(200 trails/time,10-15 minutes/time,2 times/week, all 4 weeks in the two groups;the negative and neutral words between the probe points were 20%and 80%in escape-negative-training group,and positive and neutral words between the probe points were 100%and 0 in positive-direction-training group). All the patients were evaluated by Stroop test, Self-evaluation of Anxiety Scale (SAS), Attention to Positive and Negative Information Scale (APNIS), Profile Of Mood States (POMS) and Illness Uncertainty Scale (IUS). Results After intervention, 21.4%(6/28) was alleviated in the control group, while respective 70.4%(19/27) and 44.4%(12/27) in escape-negative-training group and positive-direction-training group (χ2=8.15, P=0.003). There were no significant differences in SAS, POMS, Stroop test, APNIS and IUS among three groups (P>0.05). After intervention, the SAS, negative emotion scores in POMS (tension-anxiety, depression-dejection, fatigue-inertia, baffling-confusion) and IUS were lower in escape-negative-training group than those in control group(Q=3.79-7.58, all P<0.01);and the SAS and IUS were lower in positive-direction-training group than those in control group, while positive emotion scores in POMS (vigor-activity) higher than those in control group (Q respective was 3.11, 4.34, 6.12, all P<0.05). The SAS, POMS (tension-anxiety, depression-dejection, fatigue-inertia, baffling-confusion, vigor-activity) were more improved in escape-negative-training group than those in positive-direction-training group (Q = 3.09-4.04, all P<0.05), while no difference in IUS (P>0.05). Conclusions Attentional bias training could improve the anxiety symptoms and reduce illness uncertainty in anxious patients with coronary artery intervention treatment during transition period. Escape-negative-training is more effective in reducing patients′ negative mood and alleviating anxiety symptoms than the positive-direction-training.

Objective To investigate the efficacy of transilluminated powered phlebectomy (TIPP) and endovanous laser treatment(EVLT) combined with high ligation on treating varicose great saphenous vein.Methods A total of 238 cases with varicose great saphenous vein were divided into TIPP group (119 cases)and EVLT group (119 cases).The incidence of postoperative recovery and complications of the two groups were compared.Results There was no significant difference between the two groups on the surgery duration and postoperative recovery incident(P ＞ 0.05);the saphenous nerve injury incidence and skin impairment incidence of the TIPP group were significantly less than that of EVLT group (P ＜ 0.05);the amount of bleeding,subcutaneous hematoma incidence,and amount of surgical incision of TIPP group were significantly more than that of the EVLT group(P ＜ 0.05).Conclusions TIPP and EVLT combined with high ligation are two effective minimally invasive surgical approaches on treating varicose great saphenous vein.EVLT is with less surgical incision and less bleeding,and is more applicable for mild case;TIPP is with less operative trauma,and is more applicable for severe case.

Objective To investigate the therapeutic effects of nano-hydroxyapatite/polyamide 66/platelet-rich plasma com-pound(n-HA/PA66/PRP)on the recovery of rabbit femur bone defect.Methods 40 New Zealand rabbits were artificially made to be bone defect by resecting the 1 cm substantia ossea with periosteum of femur,and were divided into two groups averagely depen-ding on implanted materials:experimental group(n-HA/PA66/PRP),control group (n-HA/PA66).Every five rabbits were sacri-ficed on week 2,4,8,12,and the femur healing status was observed by X ray,histology,and immunohistochemistry.Results No rabbit was infected or died,no implantation objects dropped.Gross observation,X-ray result and histology results demonstrated that the experimental group began to have a new bone tissue at 2 weeks after the operation,with the extension of time,the experimental group new bone growth speed and the quantity was better than the control group.The Lane-Sandhu method X-ray score showed that the experimental group (6.80±2.05)points and the control group(4.20±1.30)points at 12 weeks after the operation,and there were significant differences between two groups(P <0.05).Immunohistochemistry indicated that expression intensity of Vas-cular endothelial growth factor at 2 weeks and 4 weeks were significant differences between two groups(P <0.05),but there was no significant difference at 8 weeks and 12 weeks (P >0.05).Conclusion PRP combined with n-HA/PA66 artificial bone could accel-erate the healing of bone defect,and the effect of repair of bone defect is better than that of n-HA/PA66 artificial bone in the early.

OBJECTIVETo explore the effect of zoledronate (ZOL) on the osteoclast adhesion and expression of integrin α(v) and β3 in vitro.

METHODSMice RAW264.7 cells were used for osteoclast differentiation in vitro, and osteoclastogenesis was examined by tartrate-resistant acid phosphatase (TRAP) staining and dentin resorption lacunae examination. The cells were then divided into 2 groups, the control group and ZOL treatment group (treated with 1 x 10(-6) mol · L(-1) ZOL for 2 d). The adhesion ability of osteoclasts and mRNA and the protein expressions of integrin α(v) and β3 were examined by crystal violet staining, real-time fluorescence quantitative polymerase chain reaction, Western blot analysis, and immunofluorescent chemistry.

RESULTSTRAP staining and dentin resorption lacunae examination revealed the formation of multi-nuclear osteoclasts. ZOL treatment significantly decreased the adhesion ability of osteoclasts (P < 0.01). In the ZOL-treated group, the mRNA levels of integrin α(v) and β3 were 0.66 ± 0.05 and 0.59 ± 0.08, respectively. In the control group, the mRNA levels of integrin α(v) and β3, were 1.01 ± 0.01 and 1.01 ± 0.02, respectively; these values were higher than those in the ZOL-treated group (P < 0.01). The protein level of integrin α(v) and β3 in the ZOL-treated group (31,934.84 ± 112.91 and 18,812.79 ± 194.13) was downregulated by approximately 39.19% and 40.17%, respectively, compared with those in the control group (52,517.81 ± 211.72 and 31,441.93 ± 456.87) (P < 0.01). Immunofluorescent examination showed that the fluorescent intensities of integrin α(v) and β3 in the ZOL-treated group (9.491 ± 0.748 and 4.744 ± 0.759) were also significantly decreased compared with those in the control group (15.159 ± 1.143 and 11.418 ± 1.095) (P < 0.01).

CONCLUSIONZOL significantly inhibits osteoclast adhesion and downregulates integrin α(v) and β3, expression, thus contributing to the ZOL-induced inhibition of osteoclast- mediated bone resorption.