Graves'ophthalmopathy(GO),also known as thyroid-associated ophthalmopathy,is an organ-specific au-toimmune disease that ranks first in the incidence of adult orbital diseases.GO has complex clinical manifestations,and dry eyes are a common cause of eye discomfort in patients with this disease.The pathogenesis of concurrent dry eyes is still unclear.It is currently believed that ocular surface damage in patients with GO is a direct factor leading to the occurrence and development of dry eyes.In addition,immunity and inflammation,and intestinal flora imbalance also play a role.Mul-tiple factors interact to form a vicious cycle,which further aggravates dry eyes.This article reviews the research results re-lated to the pathogenesis of GO complicated by dry eyes,aiming to provide ideas for clinical treatment and further research in the field.

Objective:To propose a markless patient setup workflow based on the optical surface monitoring system (AlignRT) and open-face mask immobilization for whole-course head tumor radiotherapy, assess the setup time and repositioning frequency of the proposed workflow, and conduct a comparative analysis of the differences, correlation, and consistency of the setup errors of the AlignRT and cone beam CT (CBCT) systems.Methods:A retrospective analysis was conducted for the data on the errors of 132 fractionated setup based on open-face mask immobilization of 33 head tumor patients. AlignRT-guided markless patient setup workflow was applied throughout the radiotherapy. Meanwhile, the body structures automatically generated by the treatment planning system were used as body references. The 6-degree-of-freedom (6DoF) setup errors (lateral, vertical, longitudinal, rotation, pitch, roll, and yaw directions), setup time, and repositioning frequency of the AlignRT and CBCT systems were recorded and analyzed. The Wilcoxon and Spearman analyses were used to statistically assess the differences and correlation of the setup errors of the two systems. Moreover, the Bland-Altman analysis was employed to evaluate the consistency of the two systems.Results:The 6DoF setup errors of CBCT were within the clinical tolerance (linear motions: -0.30 to 0.30 cm; rotational motions: -2.0° to 2.0°). The setup time and repositioning frequency of CBCT were (98 ± 31) s and 1.51% (2/132), respectively. There was no significant difference in setup errors between the two systems except those in x-axis ( Z = -3.11, P= 0.002), y-axis ( Z = -7.40, P<0.001), and Pitch ( Z= -4.48, P<0.001). There was a significant positive correlation between the setup errors along lateral ( rs = 0.47, P<0.001) and vertical ( rs = 0.29, P = 0.001) directions, rotation (Rtn; rs = 0.47, P<0.001), pitch (Pitch; rs = 0.28, P = 0.001) and roll (Roll; rs = 0.45, P<0.001) of the two systems. The 95% limits of agreement (95% LoA) of 6DoF setup errors were -0.12 to 0.09 cm, -0.07 to 0.17 cm, -0.19 to 0.20 cm, -1.0° to 0.9 °, -1.0° to 1.5°, and -0.9° to 1.0°, respectively. The 95% confidence interval (95% CI) of 95% LoA was -0.14 to 0.11 cm, -0.09 to 0.19 cm, -0.23 to 0.23 cm, -1.2° to 1.1°, -1.2° to 1.7°, and-1.0° to 1.1°, respectively, all of which were within the permissible error ranges. The 6DoF setup error difference of 3.41% (27/792< 5%) was beyond the 95% LoA. The maximum absolute differences of 6DoF setup errors within the 95% LoA were 0.12, 0.16, 0.19 cm, 0.9°, 1.5°, and 1.0°, respectively. Conclusions:The proposed markless setup workflow based on AlignRT combined with open-face mask immobilization for whole-course head tumor radiotherapy exhibits reasonable agreement and consistency with the patient setup using CBCT, with acceptable clinical efficiency. It can be applied to the first radiotherapy and the real-time monitoring of therapy to improve the safety and thus is of value in clinical applications.

Wutou-Gancao herb-pair is extensively used to attenuate the toxicity and enhance the efficacy of aconite. In this study, potential synergic mechanism of the herb pair was investigated by utilizing multiple ap-proaches. In silico and in vitro Caco-2 cell models were applied to study the potential binding mode of bioactive ingredients existing in liquorice with P-glycoprotein (P-gp), as well as the inhibition effects on P-gp. Additionally, anti-inflammatory activity of aconitine (AC) combined with active ingredients of liquorice, as well as pharmacokinetic patterns of AC after co-administration was investigated. Anti-inflammatory effect of AC (1 mg/kg) in rats was enhanced in combination with bioactive ingredients of liquorice (10 mg/kg). In the meanwhile, the exposure of AC in vivo was altered, in terms of Cmax and AUC. For instance, the Cmax and AUC were increased to 1.9 and 1.3 folds, respectively, when used in combination with liquiritigenin. The in silico study revealed the potential binding mode with outward facing conformation of P-gp. The resulting data obtained from transport of rhodamine-123 (Rh-123) across Caco-2 cell monolayer further indicated that the function of P-gp was inhibited by chemicals in liquorice. The synergic effect was therefore proposed to be attributed to inhibition of P-gp by liquorice since AC has been demonstrated to be the substrate of P-gp. The resuls revealed that potential synergic mechanism of Wutou-Gancao herb-pair by inhibiting function of key efflux transporter P-gp to enhance the exposure of AC in systematic circulation, and further the anti-inflammatory effect, which helps clarify the compatibility rationale of these two herbs.

Objective: To explore the relationships between the characteristics of childhood sexual abuse and non-suicidal self-injury in nursing female college students. Methods: Two medical colleges and junior colleges were selected in Anhui province. A total of 2 549 female nursing students in grade 1 to 3 were asked to fill a questionnaire regarding sociodemographic information,childhood sexual abuse and non-suicidal self-injury. Results: The reported rate of non-suicidal self-injury among female nursing students in the past six months was 8.2%. Sexual abuse at any time during childhood (primary school or earlier,middle school and high school) increased the risk of non-suicidal self-injury among female nursing students (P<0.05). Exposure to sexual abuse in all three periods was associated with 5.04(95%CI=1.73-14.62) times odds ratio than that of those who not exposed to sexual abuse (P<0.01). Only contact sexual abuse and both contact and non-contact sexual abuse in childhood were correlated with nonsuicidal selfinjury among female nursing students [OR(95%CI)=2.21(1.48-3.29), 3.56(2.13-5.96)] (P<0.05). Two patterns of sexual abuse experiences were identified,including persistent sexual abuse (3.1%) and the other group is occasional sexual (96.9%). Persistent sexual abuse in childhood was correlated to higher risk of non-suicidal self-injury compared with occasional sexual abuse (OR=2.61,95%CI=1.35-5.05,P<0.01). Conclusion The occurrence periods,types and patterns of sexual abuse in childhood are closely related to non-suicidal self-injury in female nursing students.

OBJECTIVE：To investigate the inhibitory effects of total alkaloids of Gelsemium elegans （TAG） on the proliferation and angiogenesis of human colon cancer cells. METHODS ：Human colon cancer cell line HT- 29 and HUVEC were cultured in vitro . After the intervention of low- ，medium-，high-dose TAG （40，80，120 μg/mL），the morphology of the two cells was observed by fluorescence inversion microscope. The survival rate of HT- 29 cells and HUVEC was detected by CCK- 8 assay. Flow cytometry was used to detect HT- 29 cell cycle. The migration rate ，invasion rate and tube number of HUVEC were observed by scratching test ，Transwell invasion experiment and tube formation experiment. RESULTS ：Compared with blank group ，HT-29 cells and HUVEC were decreased to different extents in TAG groups ；dead cells were observed ，and the survival rate of both decreased significantly （P＜0.05 or P＜0.01）. The proportion of HT- 29 cells at G 2/M phase in TAG groups as well as those at G 0/G1 phase in medium-dose group were increased significantly ；the proportion of HT- 29 cells at S phase in TAG groups as well as those at G 0/G1 phase in high-dose group were decreased significantly （P＜0.05 or P＜0.01）. Survival rate ，migration rate and invasion rate of HUVEC were decreased significantly in TAG groups ，and tube number was also decreased significantly at each time point during 4-24 h（P＜0.01）. CONCLUSIONS ：TAG have inhibitory effect on the proliferation of human colon cancer HT- 29 cells and HUVEC，can change HT- 29 cell cycle ，inhibit the migration ，invasion and tube formation of HUVEC.

Objective:To observe the change of the left ventricular(LV) wall shear stress (WSS) using vector flow mapping (VFM) in different segments at each phase of diastolic period among normal subjects.Methods:From August 2018 to March 2019, 200 healthy volunteers selected from the Physical Examination Center of the Second Affiliated Hospital of Harbin Medical University were recruited. The WSS values of LV segments at the same and at different phases[isovolumic relaxation period(D1), rapid filling period(D2), slow filling period(D3), atrial contraction period(D4)] in diastole were measured and analyzed.Results:①The relationships of the WSS of LV different segments at the same phase of diastolic period: The WSS values of anterior septum, posterior septum and posterior wall during D1, and the WSS values of posterior septum, posterior wall and inferior wall during D2 showed basal>middle>apical segments, the differences were statistically significant (all P<0.05). ②The changes of the WSS values of LV different segments during diastolic period: During D1-D2-D3-D4 period, the absolute values of WSS in anterior septum, posterior septum, anterior wall, lateral wall and inferior wall showed an increasing-decreasing-increasing trend. During D2-D3-D4 period, the absolute values of WSS in the posterior wall showed a decreasing-increasing trend. During D1-D2-D3-D4 period, the absolute values of WSS in the apical segment of anterior septum, basal and middle segments of posterior septum, basal, middle and apical segments of anterior wall, basal segment of lateral wall, the middle and apical segments of posterior wall, basal and middle segments of inferior wall all showed an increasing-decreasing-increasing trend, the difference was statistically significant (all P<0.05). Conclusions:The LV WSS in different segments at the same phase or in the same segment at the different phases in diastole exhibit a regular change and is consistent with the LV hemodynamic changes, which indicates that WSS can quantitatively reflect the hemodynamic changes of the LV in normal subjects.

Objective:To analyze and compare the radiation dose and image quality of kilo-voltage cone beam CT systems on different Varian accelerator platforms, providing data to support clinical decisions on selecting optimal protocols for image-guided radiotherapy based on cost-effective ratio (image quality / radiation dose).Methods:The radiation dose and image quality of various CBCT systems and scanning protocols on Varian Edge, Truebeam and ix (new and old) LINACs were obtained using a CT dose index (CTDI) phantom combined with a CT ionization chamber and a Catphan604 phantom, respectively. Figure of merit (FOM) was used to evaluate the cost-effective ratio of the image guidance schemes.Results:Considerable inter-system varieties of FOMs were observed, varying from 0.65 (Image Gently-full trajectory) to 48.46 (Image Gently-half trajectory). The inter-protocol varieties were also large, where the mean±SD was 22.14±13.47.Conclusions:Considering the explicit inter-system and inter-protocol varieties, it is clinically favorable to evaluate the image guidance schemes based on machine-specific measurement. For instance, parameters and equipment with low CTDI w can be beneficial for dose-sensitive patients. High CNR regimen favors patients with high image quality requirements. For ordinary patients, cost-effective ratio in terms of FOM can be very helpful to guide the decision-making of clinical image-guided radiotherapy.

Objective To investigate the correlation between serum carcinoembryonic antigen (CEA) levels and vascular endothelial growth factor (VEGF) levels in diabetics.Methods 92 cases of hospitalized diabetics (they were divided into the pre-treatment group and after-treatment group by intensive hypoglycemic treatment) were collected,and 94 cases of healthy controls were chosen as control group.Serum levels of CEA,hemoglobin Alc (HbAlc),VEGF and another indicators were detected and compared among the three groups.The correlations between VEGF,CEA,and HbA1c were analyzed respectively.Results The serum levels of CEA and VEGF in pre-treatment group were significantly higher than that in after-treatment group and healthy control group.In diabetics,the CEA level was positively correlated with HbA1 c (r =0.91,P ＜ 0.05) and VEGF (r =0.90,P ＜ 0.05),while there was no correlation between HbA1 c and VEGF after intensive treatment (r =0.17,P ＞ 0.05).Conclusions The level of VEGF was positively correlated with CEA,and VEGF maybe one of the pathogenesis of high CEA in diabetes mellitus.

Objective To explore the effect of Four Flavor Elimination Decoction on treatment of brain metastases.Methods Sixty patients with brain metastases,admitted to our hospital from January 2015 to January 2017,were selected.According to the willing of the patients,they were divided into observation group and control group (n=30).The patients from control group were given conventional medicines,and the patients from observation group were supplemented with Four Flavor Elimination Decoction on the basis of control group.The clinical efficacy of the two groups after treatment,and scores of Kamofsky performance status scale (KPS) and changes of T lymphocyte subsets and tumor markers before treatment and on 7th,14th,21th and 28th d of treatment were observed.Results The total effective rate of the observation group after treatment was 100％,which was significantly higher than that of the control group (50％,P＜0.05).KPS scores of the observation group were significantly higher than those of the control group on 21st and 28th d of treatment (P＜0.05).The levels of CD3+,CD4+ and CD8+ in the observation group were significantly higher than those of the control group after treatment (P＜0.05).The levels of carcino-embryonic antigen,carbohydrate antigen (CA)50 and CA125 in the observation group were significantly lower than those of the control group (P＜0.05).Conclusion Four Flavor Elimination Decoction is efficient in treatment of brain metastases,which can improve quality of life and immune indexes,and is worth of clinical application.

Objective To investigate the effects of aerobic exercise on tau phosphorylation and PI3K/ Akt pathway in the hippocampus of obese rats,and provide some theoretical basis for physical activity improving obesity-related neurological disorders.Methods Male Sprague-Dawley rats aged 3 weeks were randomly assigned to either a high-fat or a normal diet protocol for 12 weeks.Animals submitted to the high-fat diet were further divided into two groups:a sedentary group (HF-Sed) and an exercise group (HF-Ex).The rats fed the normal diet were also divided into a sedentary group (ND-Sed)and an exercise group (ND-Ex).The rats in the HF-Ex and ND-Ex groups underwent a treadmill training for 8 weeks.Then the hippocampus was isolated at 48h after the last exercise.The protein and phosphorylation levels of tau,glycogen synthase kinase 3β (GSK3β),phosphoinositide 3-kinase (PI3K) and Akt were assayed using Western blotting.Results After 12 weeks of feeding,55％ of rats in the high-fat diet group reached the conditions for the obesity model.After 8 weeks of treadmill exercises,in the HF-Sed group the phosphorylation level of tau was significanlty higher than that in the ND-Sed group,while in the HF-Ex group that was significantly lower than the HF-Sed group.Moreover,in the HF-Sed group the phosphorylation level of GSK3β Ser9 was significantly lower,and the phosphorylation level of GSK3β Tyr216 was significantly higher than the ND-Sed group,indicating the activity of GSK3β was significantly higher than the ND-Sed group.However,after 8 weeks of treadmill exercise,in the HF-Ex group the phosphorylation level of GSK3β Ser9 was signfiicantly higher,and the phosphorylation level of GSK3β Tyr216 was signficanlty lower than the HF-Sed group,indicating significantly lower activity of GSK3β than the HF-Sed group.Then,in the HF-Sed group the protein levels of PI3K p110 and p85 subunits,and the phosphorylation levels of Akt Thr308 and Ser473 were significantly lower than those in the ND-Sed group,indicating inhibited activity of the PI3K/Akt pathway.However,in the HF-Ex group the protein levels of PI3K p110 and p85 subunits and the phosphorylation levels of Akt Thr308 and Ser473 were significanlty higher than those in the HF-Sed group,showing the activity of PI3K/Akt pathway was enhanced.Conclusion Obesity induces tau hyperphosphorylation in the rats hippocampus and long-term aerobic exercises can reduce tau hyperphosphorylation by increasing PI3K/Akt pathway activity and inhibiting GSK3β activity.It has a positive effect on delaying the formation of neurofibrillary tangles and improving obesity-related neurological disorders.