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 To investigate the current status,obstacles,and specific needs associated with the application of transradial access(TRA)in peripheral interventions in Chinese hospitals,with the aim of promoting the broader adoption of TRA in interventional procedures.Methods The Committee of Interventional Oncology of China Anti-Cancer Association conducted a cross-sectional questionnaire survey to investigate and analyze the nationwide situation of TRA in peripheral interventional surgeries in 2022.Results Personnel from 60 hospitals participated in the questionnaire.The results showed that the number of peripheral interventionals performed using TRA was significantly lower than that performed using transfemoral access(TFA),with considerable variability among hospitals.The primary obstacles to the adoption of TRA were the lack of suitable catheters and the difficulty of radial artery puncture.Approximately 86.67％of the institutions expressed a high expectation for the innovation of new TRA-specific devices,particularly catheters,microcatheters,and guidewires.60.00％of medical institutions indicated a strong desire for systematic training and participation in multi-center clinical trials.Conclusions TRA peripheral intervention is feasible in many hospitals in China,however,systematic training and further promotion of TRA are essential.The innovation of new TRA-specific devices and TRA in peripheral intervention is urgent.

Objective:To observe the effect of Xuebijing injection on sepsis combined with acute gastrointestinal injury (AGI), and analyze the risk factors of sepsis combined with AGI.Methods:A retrospective cohort study was conducted. Patients with non-gastrointestinal origin admitted to the department of intensive care medicine of the First Hospital of Qinhuangdao from May 1, 2021 to October 30, 2023 were enrolled. The baseline data, source of sepsis infection, vital signs, acute physiology and chronic health evaluationⅡ(APACHEⅡ), sequential organ failure assessment (SOFA), laboratory tests, comorbidities, interventions during treatment, and the 28-day prognosis were collected. The patients were divided into Xuebijing group and non-Xuebijing group according to whether Xuebijing injection was used or not. According to whether AGI was merged or not, patients were divided into merged AGI group and non-merged AGI group. The main observational indexes were the difference in the incidence of AGI between the Xuebijing group and non-Xuebijing group and the difference in the magnitude of the decline in procalcitonin (PCT), C-reactive protein (CRP), and white blood cell count (WBC) at 7 days after admission, and the difference in the 28-day morbidity and mortality. Risk factors for AGI in septic patients were explored by univariate analysis, and statistically significant indicators were screened and included in binary Logistic regression analysis to determine independent risk factors.Results:A total of 129 patients with sepsis of non-gastrointestinal origin were enrolled, including 57 patients in the Xuebijing group and 72 patients in the non-Xuebijing group. Among 129 patients, 80 patients in the merged AGI group and 49 patients in the non-merged AGI group. There were no statistically significant differences between Xuebijing group and non-Xuebijing group in gender, age, body mass index (BMI), underlying disease, source of infection, vital sign, APACHEⅡscore, SOFA score, and clinical intervention, and there were no statistically significant differences in laboratory tests except for aspartate aminotransferase (AST) and blood urea nitrogen (BUN). The incidence of AGI was significantly lower in the Xuebijing group than that in the non-Xuebijing group [50.87% (29/57) vs. 70.83% (51/72), P < 0.05], and the 28-day mortality was slightly lower than that in the non-Xuebijing group [24.56% (14/57) vs. 30.56% (22/72), P > 0.05]. In the Xuebijing group, the decreases in CRP, PCT and WBC at 7 days after admission were greater than those in the non-Xuebijing group, with statistically significant differences in the decreases of CRP and PCT [CRP (mg/L): 47.12±67.34 vs. 7.76±111.03, PCT (μg/L): 14.08 (-1.22, 50.40) vs. 2.94 (-1.27, 14.80), all P < 0.05]. Univariate analysis showed that the use of acid suppressants, the use of analgesic sedation, the non-use of Xuebijing injections, pulmonary infections, and urinary tract infections were the risk factors for the development of AGI in patients with sepsis. Binary Logistic regression analysis further showed that the use of acid suppressants [odds ratio ( OR) = 2.450, 95% confidence interval (95% CI) was 1.021-5.883, P = 0.045], use of analgesic sedatives ( OR = 2.521, 95% CI was 1.074-5.918, P = 0.034), and urinary tract infection ( OR = 4.011, 95% CI was 1.085-14.831, P = 0.037) were independent risk factors for sepsis combined with AGI, in which the use of Xuebijing injection was a protective factor ( OR = 0.315, 95% CI was 0.137-0.726, P = 0.007). Conclusions:Xuebijing injection reduced the incidence of AGI in patients with non-gastrointestinal sepsis. PCT and CRP decreased more markedly than in patients who did not use Xuebijing injection. The use of acid-suppressing agents, analgesic and sedative agents, and urinary tract infections were independent risk factors for sepsis in combination with AGI, while the use of Xuebijing injection is a protective factor.

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 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.

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 study the discrepancy influence of the sulbactam content on susceptibility testing results of cefoperazone/sulbactam combination disks.Methods Agar dilution method was used to determine MICs of cefoperazone,cefoperazone/sulbactam(2:1 and 1:1),and disk diffusion was used to detect the zone diameters of cefoperazone,cefoperazone/sulbactam(75/30 and 75/75μg/disk)disks against 534 clinical gram-negative isolates.The discrepancy within the results of MICs,zore diameters,the method of agar dilution and disk diffusion was analyzed.Results By standard agar dilution method,MIC_(50) of cefoperazone,cefoperazone/sulbactam(2:1 and 1:1)were 32,16,16μg/ml,and MIC_(90) of those were ≥256.128,64 μg/ml respectively.No statistic discrepancy was found for MICs between the ratios of 2:1 and 1:1 combination by Wilcoxon ranks test(Z=-0.248,P=0.804).Susceptibility rate,resistance rate,and intermediate rate with 75/30μg disk were 55.3%,24.5%and 20.2%respectively,which were similar to those determined by agar dilution method.Susceptibility rate,resistance rate,and intermediate rate(I%)with 75/75μg disk were 72.5%,12.4% and 15.1% respectively,compared with the susceptibility rate from 75/30μg disk was 17.2% higher.Statistic discrepancy were tested by paired t-test (t=21.613,P＜0.01)with two groups of whole strains' zone diameters from 75/30μg and 75/75μg disks,and resulting in the difference of susceptibility or resistance rates for ESBL-producing strains,Acinetobacter bauamnnii and Enterobacteriaceae without ESBL tested isolates.On the contrary,for Pseudomonas aeruginosa,Stenotrophomonas maltophilia and ESBL negative isolates,the zone diameters discrepancy was not statistically significant between the results from 75/30μg and 75/75μg disks.Conclusions There is no statistic discrepancy between the susceptibility results from cefoperazone/sulbactam(2:1 or 1:1 ratios)in dilution method and in diffusion method with 75/30μg disk.When the 75/75μg disk is used to be tested for ESBL-producing strains,Acinetobacter bauamnnii and other Enterobacteriaceae,the results should be shown with sulbactam content.