Circular RNA(circRNA) is a type of RNA with a circular coding structure, characterized by a circular topological structure formed during the RNA splicing process. Compared to traditional linear mRNA, circRNA exhibits enhanced stability and immunogenicity, leading to its wide-ranging potential applications in areas such as vaccines, biomarkers, and targeted therapies. This paper summarizes the research progress of circRNA, including its synthesis and degradation in vivo and in vitro, components, biological functions, and applications, aiming to provide novel insights for their utilization in vaccine design and development.

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 explore a method for detecting the integrity of target nucleic acid in recombinant adeno-associated virus(rAAV),and establish a preliminary analysis algorithm.Methods The free DNA fragment of rAAV was digested,and the virus genome was extracted.Five pairs of overlapping primers were designed,using the orthogonal array method,which were detected by digital PCR respectively,with conventional conditions:20 μL reaction system with EveGreen and4 μL template,and digital PCR conditions:95 ℃ 5 min;95 ℃ 15 s,55 ℃ 30 s,72 ℃ 90 s for 45 cycles.The enhancement condition of ultra-long nucleic acid fragment was 25 μL reaction system with Mix B-2 000 bp and 2 μL template,and the quantitative analysis was performed by using the software attached to the instrument.Using the least square method,the number of full-length fragments was fitted and analyzed,and then the integrity distribution of target nucleic acid was interpreted.Results The fragments with the distance between primers of no more than 1 200 nt were amplified effectively,and a series of effective copies of fragments with a length of about 1 000 nt were obtained by systematic analysis.The copy number of common fragments was fitted and analyzed by the least square method.It was estimated that the full-length fragments in the sample were no more than 1 234 copies/μL,and there was a signficant difference(P < 0.05)between this value and the maximum measured value of 1 443 copies/μL,with the difference of approximately 16.9%.Conclusion A preliminary detection method for the integrity of target nucleic acid in rAAV has been developed,and a certain amount of incomplete target nucleic acids were analyzed in the test sample,laying a foundation for further in-depth research.

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.

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.

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.

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.

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.

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.