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.

Venous system diseases mainly include varicose veins and venous malformations of lower limbs and the genital system. Most of them are chronic diseases that cause serious clinical symptoms to patients and affect their health and quality of life. Sclerotherapy has become the first-line therapy for venous system diseases. However, there are problems such as incomplete fibrosis and vascular recanalization after sclerotherapy, and improper operation will cause serious adverse consequences. Therefore, exploring a safe and effective sclerotherapy strategy is essential for developing clinically successful sclerotherapy. To solve the above problems, we proposed a new sclerotherapy strategy with a dual mechanism of "vascular damage and plasmin (PLA) system inhibition." We intended to construct a novel cationic surfactant (AEO_x-TA) by reacting tranexamic acid (TA), a parent structure, with fatty alcohol polyoxyethylene ether (AEO_x) by ester bonds. AEO_x-TA could damage vascular endothelium and initiate a coagulation cascade effect to induce thrombus. Furthermore, AEO_x-TA could be degraded by esterase and release the parent drug, TA, which could inhibit the PLA system to inhibit the degradation of thrombus and extracellular matrix and promote the process of vascular fibrosis. In addition, such surfactant-based sclerosants have foam-forming properties, and they can be blended with polyvinyl alcohol (PVA) to prepare a highly stable foam formulation (AEO_x-TA/P), which can achieve a precise drug delivery and prolonged drug retention time, thereby improving drug efficacy and reducing the risk of ectopic embolism. Overall, the novel cationic surfactant AEO_x-TA provides a new avenue to resolve the bottleneck: surfactant sclerosants' efficiency is relatively low in the current sclerotherapy.

OBJECTIVE Parkinson's disease(PD)is a progressive neurodegenerative disease clinically char-acterized by dyskinesia,tremor,rigidity,abnormal gait,whereas 90%of patients with PD suffer from defects of the sense of smell before the appearance of the motor dysfunctions.However,the mechanism of olfactory disor-der is still not clear.METHODS We utilized olfaction based delayed paired association task in head-fixed mice.We focused on functional role of neural circuit using opto-genetic techniques.In addition,we viewed the synaptic transmission by slice physiological recording and count-ed the cell number of targeted circuits.RESULTS AND CONCLUSION In our experiments,olfactory working memory impairments were found in the PD mice,and the working memory impairment appeared before motor dys-functions.Furthermore,we also investigated the functional role of neural circuit for olfactory working memory in PD mice.Meanwhile,the excitatory post synaptic currents were decreased as a result of presynaptic release proba-bility suppression in PD mice.However cell loss wasn't found in working memory related circuit recently.These will provide a new idea of clinic diagnosis for PD.

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 provide reference for the R&D of TCM patents for treating gastric cancer and layout. METHODS：TCM patents for treating gastric cancer collected by the State Intellectual Property Office and the European Patent Office Espacenet were retrieved from the inception to Dec. 31st， 2019. After the initial examination ，a second search was conducted based on the keywords such as “Stomachache”“Fuliang” “Accumulation”“Cancer of stomach ”“Gastric”and their synonyms. Each literature was read one by one and screened manually. Excel 2007 software was used to input general information of included patents. SPSS modeler 15.0 software and SPSS 22.0 software were used for association rule analysis and hierarchical cluster analysis of TCM used more than 30 times and top 30 frequently used. Based on patent analysis ，internal strength （S），weakness（W），external opportunity （O）and threat （T）of TCM for treating gastric cancer were analyzed ；based on this ，four different types of combination strategies were formulated. RESULTS & CONCLUSIONS ：Finally，385 patents were obtained ，including 379 domestic patents （98.44％） and 6 foreign patents （1.56％）. The number of patent applications and applicants of TCM for treating gastric cancer in China was on the rise during 1994-2016. The commonly used TCM for treating gastric cancer were mainly tonifying deficiency drugs and heat clearing drugs ， and the meridian tropism were mostly the stomach meridian and spleen meridian. According to the efficacy ，the commonly used drug combinations include the combination of tonifying spleen and Qi ，the combination of anti-cancer and detoxification ，and the combination of drying dampness and resolving phlegm. The results of hierarchical cluster analysis showed that Poria cocos ， Atractylodes macrocephala ，Astragalus membranaceus ，Scutellaria barbata ，Hedyotis diffusa and Glycyrrhiza uralensis were clustered into one category and the common combination for treating gastric cancer. The remaining cluster distributions are also in line with the characteristics of TCM syndrome differentiation and treatment. Strength of domestic TCM patents for treating gastric cancer were that the number of patents in China was taking a leading position in the world ，the patent system of key applicants was mature，the combination of compound patents embodied the characteristics of disease and dialectical theory. Weakness included low patent authorization rate ，to-be-improved effectiveness and safety studies of TCM patents ，weak development of TCM extract patents，low degree of patent internationalization and hanging same-family patents. Opportunities were that the demand for drugs for gastric cancer was increasing with each passing day ，and natione actively support the development of the TCM industry. Threats were that competitors in the international market had the potential to seize the market. The development of TCM for treating gastric cancer in China should take market demand and national policy support as an opportunity ，learn from TCM patent characteristic system of key applicants ，continue to give full play to the advantages of TCM in prevention and syndrome differentiation of disease，pay more efforts to the development of weak links such as TCM extracts ，safety and effectiveness ，improve the international competitiveness in the field of patents ，while establish a warning and navigation analysis system for patents to effectively reduce the intellectual property threats and risks of invention patents of China in the international environment.

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 In this study,we explored the role of combination of autophagy inhibition and anti-VEGF in proliferation,migration and tube formation of mouse retinal vascular endothelial cells(RVECs). Methods Well cultured mouse RVECs were randomly divided into four groups:autophagy inhibition group(add-ing autophagy inhibitor 3-MA),anti-VEGF group(adding anti-VEGF-A neutralized antibody),autophagy inhibi-tion+anti-VEGF group(adding the two reagents)and the control group.All cells were then cultured in the hypoxic condition. The cell proliferation,migration and tube formation were detected by EdU,transwell and matrigel as-say,respectively. Results The cell proliferation rate,number of migrated cells and number of tube formation of the other three groups decreased when compared with the control group.These data above in autophagy inhibition+anti-VEGF group were all significantly less than 3-MA group and anti-VEGF group. Conclusion Combination of autophagy inhibition and anti-VEGF may be more effective than simple anti-VEGF in inhibition of retinal neovascu-larization.

Objective To analyze the antibiotic resistance of clinical isolated bacteria in elderly inpatients in Beijing Hospital from 2006 to 2008.Methods A total of 5710 strains isolated from elderly inpatients received antibiotic sensitivity test (AST) by using K-B method, and the data were analyzed with WHONET 5.4 software.Results During the 3 years, in constituent ratio of bacteria, P.aeruginosa, E.coli and Stenotrophomonas maltophilia were at the top of gram-negative bacteria.And S.aureus, coagulase-negative Staphylococcus (CONS), S.pneumoniae and Enterococcus spp.were at the top of gram-positive bacteria.The results of AST in vitro showed that 19 of 121 strains of S.pneumoniae were penicillin-insensitive S.pneumoniae (PNSP).In 690 strains of S.aureus, the methicillin-resistant S.aureus (MRSA) ratio was 80.2%, and vancomycin-insensitive strains were not found.And 114 strains of Enterococeus faecalis and 95 strains of Enterococcus faecalis were isolated, while the antibiotic resistance of the latter was stronger than the former, and 19 strains were vancomycin-resistant strains.The detection ratios of E.colt producing ESBLs were 41.7%, 55.0% and 56.8%, and the detection ratios of Klebiella pneumonia producing ESBLs were 16.0%, 22.4% and 27.3 %.The antibiotic resistance of ESBL-producing bacteria was much stronger than non-ESBLs producing bacteria.Multi-antibiotic resistant strains of Pseudomonas aeruginosa and Acinetobacter spp.were found.Conclusions It is necessary to detect the drug-resistant strains periodically for understanding the changes in bacterial resistance and providing a theoretical basis for the medication by the clinical experience.

Objective To explore the repair of the open compound wounds in lower extremities caused by multiple factors. Methotis Transplantation of cutaneous.musculo-cutaneous or greater omentum flaps were applied to 155 patients of open compound lower extremity wounds. Results The wound healing rate following first operation was 50% and that following two operations was 14.8%.While the wounds were healed in 7.7% of patients after three operations. Conclusion Transplantations of cutaneous,musculo-cutaneous or greater omentum flaps ale effective to repair and reconstruct the open compound lower extremity wounds.