Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as ¹⁷⁷Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of ¹⁷⁷Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, ¹⁷⁷Lu-LNC1010, for PRRT. In preclinical studies, ¹⁷⁷Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of ¹⁷⁷Lu-LNC1010 in patients with advanced/metastatic NETs. ¹⁷⁷Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of ¹⁷⁷Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two ¹⁷⁷Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.

OBJECTIVE To explore the mechanism by which gastrodin improves renal hyperten-sion in rats.METHODS A rat model of renal hypertension was established by ligating the renal artery.seventy-five rats were randomly divided into 5 groups(n=15):control group(sham operation group),model group,model+ramipril 1 mg·kg-1,model+gastrodin 100 and 200 mg·kg-1.The systolic blood pressure of the tail artery after modeling>18.12 kPa was regarded as the success of modeling.After the model was established,rats in the model+ramipril group were ig given ramipril 1 mg·kg-1 while the model+gastrodin group was ig given gastrodin 100 and 200 mg·kg-1 respectively for 4 weeks.Colori-metric assay kit was used to detect the serum superoxide dismutase(SOD)activity and malondialde-hyde(MDA)content in rats.ELISA was used to detect serum angiotensin-2(Ang-2)and aldosterone(ALD)contents,as well as serum and thoracic aortic tissue interleukin-1β(IL-1β),IL-6 and tumor necrosis factor α(TNF-α)content.HE staining was performed to detect pathological changes in thoracic aorta tissue of rats.The expressions of autophagy protein miceotubule associated protein light chain 3(LC3)-Ⅱand LC3-Ⅰwere detected by Western blotting.RESULTS The systolic pressure of the tail artery of rats after modeling exceeded 18.12 kPa,indicating that the modeling was successful.Compared with the control group,the contens of Ang-2(P<0.01)and ALD(P<0.01)in the model group were significantly increased,the activity of SOD(P<0.01)in serum and thoracic aorta tissue was significantly decreased,the content of MDA(P<0.01)was significantly increased,the contents of IL-1β,IL-6 and TNF-α in serum and thoracic aorta tissue were significantly decreased(P<0.01)and the ratio of LC-32/LC-31 in thoracic aorta tissue was significantly increased(P<0.01).Compared with the model group,gastrodin significantly increased the systolic pressure of the tail artery(P<0.01),the contents of Ang-2(P<0.01)and ALD(P<0.01)and the activity of SOD(P<0.01)in serum,as well as decreased the contents of MDA,IL-1β,IL-6 and TNF-α(P<0.01)in serum and thoracic aorta tissue.Meanwhile,gastrodin signifi-cantly decreased the ratio of LC3-Ⅱ/LC3-Ⅰ in rat thoracic aorta(P<0.01).CONCLUSION Gastrodin can improve the blood pressure of renal hypertensive rats,and the mechanism is possibly related to the reduction of autophagy protein LC3-Ⅱ/LC3-Ⅰratio.

Tumor metastasis depends on the dynamic balance of the actomyosin cytoskeleton. As a key component of actomyosin filaments, non-muscle myosin-IIA disassembly contributes to tumor cell spreading and migration. However, its regulatory mechanism in tumor migration and invasion is poorly understood. Here, we found that oncoprotein hepatitis B X-interacting protein (HBXIP) blocked the myosin-IIA assemble state promoting breast cancer cell migration. Mechanistically, mass spectrometry analysis, co-immunoprecipitation assay and GST-pull down assay proved that HBXIP directly interacted with the assembly-competent domain (ACD) of non-muscle heavy chain myosin-IIA (NMHC-IIA). The interaction was enhanced by NMHC-IIA S1916 phosphorylation via HBXIP-recruited protein kinase PKCβII. Moreover, HBXIP induced the transcription of PRKCB, encoding PKCβII, by coactivating Sp1, and triggered PKCβII kinase activity. Interestingly, RNA sequencing and mouse metastasis model indicated that the anti-hyperlipidemic drug bezafibrate (BZF) suppressed breast cancer metastasis via inhibiting PKCβII-mediated NMHC-IIA phosphorylation in vitro and in vivo. We reveal a novel mechanism by which HBXIP promotes myosin-IIA disassembly via interacting and phosphorylating NMHC-IIA, and BZF can serve as an effective anti-metastatic drug in breast cancer.

ObjectiveHigh performance liquid chromatography （HPLC） was used to establish the specific chromatograms of Aurantii Fructus from different origins， and the quality variability of Aurantii Fructus from Sichuan was analyzed and evaluated by combining entropy weighting method and grey correlation method. MethodHPLC was performed on an Agilent Eclipse Plus C₁₈ column （4.6 mm×250 mm， 5 μm） with a gradient elution of methanol （A）-0.1% phosphoric acid aqueous solution as the mobile phase （0-12 min， 25%-33%A； 12-21 min， 33%-41%A； 21-30 min， 41%-42%A； 30-40 min， 42%-59%A； 40-53 min， 59%-72%A； 53-60 min， 72%A； 60-65 min， 72%-100%A； 65-70 min， 100%A； 70~71 min， 100%-25%A； 71-80 min， 25% A） at a flow rate of 1.0 mL·min^-1， the injection volume was 10 μL and the detection wavelength was 330 nm. Fifty batches of Aurantii Fructus samples from different origins （Sichuan， Chongqing， Jiangxi and Hunan） were tested， and the similarity evaluation software is used to generate characteristic profiles and compare them with control profile for peak identification， and then to evaluate the similarity of the samples. IBM SPSS 19.0 and SIMCA 14.1 were used to perform multivariate statistical analysis on the results of the samples， and then the entropy weighting method and grey correlation were used to calculate the overall quality score of samples from Sichuan. ResultHPLC specific chromatogram of Aurantii Fructus was established， and 14 common peaks were identified as eriocitrin， neoeriocitrin， narirutin， naringin， hesperidin， neohesperidin， meranzin hydrate， poncirin， meranzin， marmin， nobiletin， 3，3′，4′，5，6，7，8-heptamethoxyflavone， tangeretin and auraptene. And the similarities between the samples from Sichuan and the control chromatogram were all above 0.980. The samples could be classified into four categories according to their main origins by chemical pattern recognition， and the results of cluster analysis， principal component analysis and orthogonal partial least squares-discriminant analysis were all able to discriminate the samples of different main origins effectively. The comprehensive evaluation results of entropy weighting method combined with grey correlation showed that the quality of Aurantii Fructus from Sichuan varied greatly among different origins， and the quality of Aurantii Fructus from Sichuan was ranked as Bazhong>Luzhou>Chongqing>Neijiang. ConclusionIn this study， the characteristic mapping of Aurantii Fructus from Sichuan is established， and combined with the analytical methods of chemometrics and grey correlation， the quality of samples from different origins can be effectively differentiated， which can provide a reference for the comprehensive evaluation and control of the quality of Aurantii Fructus from Sichuan.

Objective:To compare the prediction efficiency of traditional linear regression model and four machine learning models on the learning behavior of clinical medical postgraduates, and to explore the pros and cons and applicability of different prediction models.Methods:A total of 6,922 clinical medical postgraduates were surveyed, their comprehensive learning behavior scores were obtained through the learning behavior scale. In the training set, Lasso linear regression and artificial neural network, decision tree, Bootstrap random forest, and lifting tree were used to build prediction models respectively. The above models were used to predict the validation set data and compare the prediction efficiency.Results:The comprehensive learning behavior score of clinical medical postgraduates was (3.31±0.54) points, and the overall compliance rate was 74.02%. In the linear regression model, the influence of age, school level, degree type, learning interest, pressure and satisfaction on learning behavior were statistically significant. In the prediction of validation set, the sensitivity, specificity, and accuracy of the linear regression model were 0.484, 0.914, and 0.801, respectively. The indexes of the four machine learning models were higher than those of the traditional linear regression model, and the Bootstrap random forest had the highest elevation.Conclusion:The linear regression model has a good prediction effect on learning behavior, and machine learning is superior to linear regression model in terms of accuracy of prediction. However, traditional linear regression models are superior to machine learning models in computational efficiency and interpretability.

Objective : To understand the epidemiological characteristics of injury deaths among residents in Taizhou,and to provide evidence for prevention and control of injury death. Methods : The monitoring data of injury deaths in Taizhou residents from 2010 to 2016 were derived from the Chronic Disease Surveillance Information Management System of Zhejiang Province. Descriptive epidemiological methods were used to analyze injury mortality,cause of death,population characteristics and life lost due to injury. Results : From 2010 to 2016,a total of 26 313 injury death cases were reported in Taizhou,with an average annual injury mortality rate of 63.61/100 000 and a standardized rate of 56.64/100 000; the mortality rate of injury from 2010 to 2016 showed a downward trend year by year（P<0.05）,and the annual change percentage（APC）was -7.1%. The mortality rates of 0-14 years old,15-44 years old,45-64 years old,65 years old and above group were 15.37/100 000,22.45/100 000, 69.64/100 000 and 315.69/100 000. There were statistically significant differences in the mortality rates of residents between different age groups （P<0.05）. Except for there were no statistically significance differences between the mortality rates of 15-44 years old and 0-14 years old in 2013 and 2014（both P>0.008 3）. The mortality rate in each year from 2010 to 2016 were decreased by 0-14 years old,15-44 years old,45-64 years old,65 years old and above group （all P<0.008 3）. The mortality rate of all age groups showed a downward trend year by year（P<0.05）. The top five injury death causes were accidental falls（17.97/100 000）,motor vehicle traffic accidents（13.97/100 000）,drowning（5.59/100 000）,suicide （5.25/100 000）,other accidents and harmful effects（4.50/100 000）,accounting for 84.35% of the total number of deaths. The injury death causes of the 0-14 years old group were mainly drowning,which was 407 cases,accounting for 1.55% of the total number of deaths; for 15-44 years old group and the 45-64 years old group,the main causes were motor vehicle traffic accidents,which were 1 373 and 2 354 cases,accounting for 5.22% and 8.95%,respectively; for 65 years old and above group,the main cause was mainly accidental falls,which was 6 777 cases,accounting for 25.76%. The years of potential life lost （PYLL） due to injury was 328 678 person-years and the years of potential life lost rate （PYLLR） was 7.95‰. Conclusion The injury mortality rates of Taizhou residents were declined from 2010 to 2016. The mortality rate of elderly residents due to injury were high and accidental falls was the main cause of injury deaths.

Objective To investigate the correlation between the expression of phospholipase Cβ1 (PLCβ1) and the clinical relevant parameters and prognosis in patients with hepatocellular carcinoma (HCC).Methods By using tissue microarray technique and immunohistochemical method,the expressions of PLCβ1 in tumor and pericancerous tissues were tested in 141 HCC patients.The relationship between the expressions of PLCβ1 and the clinical and pathological characteristics was analyzed.Colony formation assay and apoptosis experiments were used to check the effect of PLCβ1 on proliferation of HCC cells.KaplanMeier analysis and Cox multivariate regression model analysis were adopted to analyze the prognosis of HCC patients.Results The expression level of PLCβ1 in tumor tissues was obviously higher than that in pericancerous tissues,which was closely related to the tumor staging.Kaplan-Meier survival analysis indicated that the survival rate in HCC patients with high expression level of PLCβ1 was lower than that in HCC patients with low expression level of PLCβ1.Cox multivariate regression analysis revealed that high expression of PLCβ1 was an independent prognostic factor for HCC patients.Over expression of PLCβ1 in HCC cells could promote the proliferation of HCC cell and inhibit its apoptosis.Further investigation showed that activation of extracellular regulated protein kinase signaling pathway might be involved in PLCβ1-mediated HCC cell growth.Conclusion PLCβ1 can promote the progression of HCC,and the expression level of PLCβ1 can be regarded as an independent prognostic factor for HCC,and it is expected that PLCβ1 may become an ideal therapeutic target.

Objective To investigate the influence of sorafenib on the expressions of B7-H3 and B7-H4 proteins in different human hepatocellular carcinoma cell lines,including HepG2,Hep3B,BEL-7402,BEL-7404,BEL-7405,QGY-7701,QGY-7703,SMMC-7721,MHCC97H,MHCC97L,HCCLM3 and HCCLM6.Methods Western blotting and MTT assay were used to check the influence of sorafenib on the expressions of B7-H3 and B7-H4 proteins in different human hepatocellular carcinoma cell lines and to test the inhibitory effect of sorafenib on different human hepatocellular carcinoma cell lines.Results Compared with normal human liver cells (HL-7702),the expressions of B7-H3 and B-H4 proteins in different human hepatocellular carcinoma cell lines were significantly up-regulated (P＜0.01).The cytotoxic activity IC50 values of sorafenib to Hep3B,BEL-7404,MHCC97H,HCCLM3 and HCCLM6 were 14.56,9.14,9.46,17.21 and 9.29 μmol/L respectively.After treating Hep3B,BEL-7404,MHCC97H,HCCLM3 and HCCLM6 with sorafenib at the doses of 5,10 and 20 μmol/L separately,the expressions of B7-H3 and B7-H4 proteins were strikingly down-regulated when compared with the control group (P＜0.01).Conclusion The overexpressions of B7-H3 and B7-H4 proteins in different human hepatocellular carcinoma cell lines are a common finding,which can influence tumor immune escape.It may be a new target for prevention and treatment of liver cancer in future.

Objective:To investigate the mastery and application of medical ethics basic knowledge in geriatric ward medical staffs,and the way which they receive relevant education. Methods:From November 2016 to January 2017,240 questionnaires about medical ethics were distributed among medical staffs in clinical department in the Chinese PLA General Hospital,among them,30 were medical groups and 210 were nursing groups;and a total of 233 valid questionnaires were collected. The nurses were divided into geriatric ward nursing group and non - geriat-ric ward nursing group,according to whether they work in the geriatric wards or not. Results:Only 2. 14％ and 7. 72％ participants fully and correctly answered the core concepts and basic principles of medical ethics,respec-tively. The rate of informed consent in medical staffs in geriatric group was significantly higher than that of non -geriatric group (92. 66％ vs 82. 11％ ,P = 0. 02);the patient' s privacy protection in geriatric nursing group was significantly higher than that of non - geriatric nursing group (92. 66％ vs 31. 57％ ,P < 0. 001). 28. 75％ of the respondents received medical ethics continuing education curriculum,and the proportion of correctly receiving ex-pectable death in these medical staffs (71. 40％ ) was significantly higher than that of other education pathway groups (36. 17％ ). Conclusion:Medical staffs lack more knowledge on medical ethics. Clinical work in geriatric medicine has higher demand for medical ethics knowledge,and continuing medical education can help to improve the cognitive level of medical ethics in medical staffs.

Objective To compare the technical success ,complication rates and comfort of the radiologic placement of central venous ports(CVP) via the internal jugular vein ,subclavian vein via subclavian region ,subclavian vein via supraclavicular region un‐der DSA guidance .Methods We retrospectively reviewed 188 CVP patients implanted at hospitals between December 2012 and De‐cember 2013 .The patients were divided into three groups according to the different catheter implantation sites ,internal jugular vein (group A) ,subclavian vein via subclavian region (group B) and subclavian vein via supraclavicular region (group C) .Intraoperative pain score ,technical success rates ,peri‐procedural ,as well as early and late complication rates were recorded based on the image fol‐low‐up and patient medical records .Results The technical success rate was 100 .0% without any lethal complications .The CVP re‐lated infections were occurred in each group with 1 patient ,but there was no statistics significant different(P>0 .05) .Subclavian vein thrombosis were occurred 2(2 .1% ,2/96) in group B ,which was recanalized after thrombolytic therapy ,and 1(1 .7% ,1/60) in group C ,which was completely occluded .The higher rate of catheter migration and kinking of catheter were occurred in group A and group C .The rate was statistically significant difference among the three groups (P<0 .01) .The late complication rates were statistically higher in group A and C compared with group B (P<0 .05) .The punch‐off was just occurred in group B (n=2) .There were no significant differences about catheter fracture ,port rotation and wound dehiscence among the three groups(P>0 .05) .Con‐clusion In DSA radiologic placement of a CVP via the subclavian vein via subclavian region is safe and efficient with more comfort‐able and lower complication rates ,which could be chosen priority .