OBJECTIVE To prepare Arg-Gly-Asp（RGD）-modified doxorubicin （DOX）-loaded “core-shell” nanoparticles （RGD@DOX-LPNs）， characterize the nanoparticles， and investigate their antitumor effects. METHODS RGD@DOX-LPNs were prepared using the nanoprecipitation method. Their morphology was examined by visual inspection and electron microscopy. Particle size， polydispersity index （PDI）， and Zeta potential were determined， and differential scanning calorimetry （DSC） and X-ray diffraction （XRD） were employed. Encapsulation efficiency （EE）， drug loading （DL）， and stability were evaluated. The in vitro release kinetics， mucus diffusion， and tumor cell uptake [tracked using coumarin 6 （COU）] were investigated. The in vivo tissue distribution and gastrointestinal retention [labeled with 11-chloro-1， 1′-dipropyl-3， 3， 3′， 3′-tetramethyl-10， 12- trimethyleneindotricarbocyanine iodide （IR780）] were investigated. Using 4T1 tumor-bearing mice as the experimental subjects， the effects of the prepared formulation on tumor volume， tumor weight， and cell apoptosis rate were evaluated. RESULTS RGD@DOX-LPNs presented as orange transparent liquid with uniform and near-spherical particles. The particle size was （159.67± 8.02） nm， PDI was 0.15±0.06， and Zeta potential was （－19.70±0.79） mV. After modification with RGD， the thermal absorption peak and crystalline diffraction peak of DOX disappeared. EE and DL of RGD@DOX-LPNs were （72.65±4.37）% and （4.62± 0.38）% ， respectively. No obvious changes in appearance， particle size， or EE were observed after storage at 4 ℃ and 25 ℃ for 7 days. The cumulative drug release at 4 h was approximately 73%， which was lower than that of free DOX（almost completely released within 1 h）. The amount of COU in the first segmental mucus layer of COU-LPNs was significantly lower than that in the corresponding segment of RGD@COU- LPNs， whereas it was significantly higher in the 2nd to 5th segmental mucus layers compared to RGD@COU-LPNs （P＜0.01）. Cellular uptake of RGD@COU-LPNs was significantly higher than that of COU-LPNs（P＜0.05）. The isolated tissue fluorescence intensity of RGD@IR780-LPNs was stronger than that of IR780-LPNs， indicating better small intestinal retention. Compared with free DOX and unmodified nanoparticles （DOX-LPNs）， RGD@DOX-LPNs exhibited a higher tumor inhibition rate of 65.74%， significantly reduced tumor volume and weight， and increased apoptosis rate（P＜0.01）. CONCLUSIONS RGD@DOX-LPNs are successfully prepared with sustained release properties， which can improve gastrointestinal mucus retention， enhance cellular uptake of DOX， and have potent antitumor activity against breast cancer.

AIM: To observe the changes of corneal densitometry(CD)and higher-order aberrations after small incision lenticule extraction(SMILE), and to explore their correlations and influencing factors.METHODS: Prospective study. A total of 62 high-degree myopia and compound myopic astigmatism patients(62 eyes)who underwent SMILE in Urumqi Aier Eye Hospital from December 2022 to November 2023 were collected. The CD, root mean square of corneal higher-order aberrations(RMS HOA), spherical aberration, vertical coma, horizontal coma, and corneal epithelial thickness(CET)of the patients were measured before surgery, and at 1 d, 1 wk, 1, 3, and 6 mo after surgery, respectively.RESULTS:There were 4 patients lost to follow-up during the period, all due to failure to attend scheduled reexaminations. The number of complete and valid cases was 58 eyes. The CD in the central and paracentral regions of the anterior, middle, and total layer of the cornea increased significantly on the first day after surgery(all P<0.003). At 6 mo after surgery, there was a slight but statistically significant decrease in the CD of the central and paracentral regions of the anterior and the total anterior layer(all P<0.003). Compared with the preoperative baseline values, the RMS HOA, spherical aberration, and vertical coma significantly increased at 6 mo after surgery(all P<0.003), while the change in horizontal coma was not statistically significant. Compared with the preoperative baseline values, the CET in the central, paracentral, and peripheral regions of the cornea, as well as the total average CET in the 0-7 mm range of the cornea increased at 6 mo after surgery(all P<0.003). At 1 d after surgery, CD of the anterior layer and total layer in the central region of the cornea were positively correlated with the CET in the central region(rs=0.327, rs=0.250, all P<0.05). At 6 mo after the surgery, the CD of the middle layer and posterior layer in the central corneal region were negatively correlated with the preoperative spherical equivalent and the change of RMS HOA(all P<0.05).CONCLUSION:The anterior CD decreases at 6 mo after SMILE for high myopia correction, and there is a certain correlation between the changes in CD and some clinical parameters.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

Objective To compare and analyze the application value of domestic Octoparms and imported Celect inferior vena cava filter(IVCF)in the interventional treatment of venous thromboembolism(VTE).Methods Forty patients with VTE were randomly divided into Octoparms group(experimental group)and Celect group(control group)according to the double-blinded method of the central random system.All the patients underwent filter placement,catheter-directed thrombolysis and filter retrieval.The primary end point was the success of filter placement and retrieval,and the secondary end point included indwelling complications such as the occurrence of pulmonary embolism(PE)and filter tilt and migration.Results Forty patients were enrolled in this study,22 patients and 18 patients were divided into the experimental group and the control group,respectively.Among them,11 cases were identified with right lower extremity deep vein thrombosis,29 cases with left lower extremity deep vein thrombosis,17 cases with PE,and 6 cases with inferior vena cava thrombosis.The success rate of IVCF placement was 100%in all participants.Immediately after filter place-ment,the angle of filter tilt was(3.8±2.3)° in the experimental group and(4.9±2.8)° in the control group(t=1.44,P=0.16).Filter retrieval was successful in 21 cases(21/22,95.5%)of the experimental group and 17 cases(17/18,95.5%)of the control group.There was no significant difference between the two groups(t=0.14,P=0.89).The mean indwelling time of filter was(8.0±2.1)days in the experimental group and(9.7±3.1)days in the control group(t=0.73,P=0.47).The angle of filter tilt was(5.3±3.4)° in the experimental group and(5.7±7.7)° in the control group(t=0.19,P=0.85).There was no significant difference for filter placement and retrieval between the two groups(t=0.48 and 2.00,P=0.06 and 0.64,respectively).There were no complications of filter migration,strut penetration or new PE in both groups.Conclusion The application value of domestic Octoparms and impor-ted Celect IVCF is similar in interventional treatment of VTE.

A precursor ion selection (PIS) based ultra high performance liquid chromatography-quadrupole time of flight mass spectrometry (UHPLC-Q-TOF-MS) analytical method was used to screen the chemical components in Jiawei Dingzhi pills (JWDZP) comprehensively and rapidly. To compile the components of the compound medicine, a total of 1 921 components were found utilizing online databases and literature. After verifying the sources, unifying the component names, merging the multi-flavor attributed components, and removing the weak polar molecules, 450 components were successfully retained. The Acquity UPLC HSS T3 column (100 mm × 2.1 mm, 1.8 μm) was used, with a 0.1% formic acid water (A)-acetonitrile (B) as the mobile phase. The flow rate was 0.35 mL·min^-1, the column temperature was 35 ℃, and an electrospray ion source was used. Data was collected with the PIS strategy in both positive and negative ion modes. Compounds were screened through matching accurate molecular weight of the database, and identified according to MS/MS data (characteristic fragment ions and neutral loss), with comparison of reference. Some compounds were confirmed using standard products. A total of 176 compounds were screened out in the extract of JWDZP, among which 26 compounds were confirmed by standard products. These compounds include 96 components from the sovereign drug, and 34 coefflux components with low ion intensity. The PIS-UHPLC-Q-TOF-MS/MS method established in this study can quickly and comprehensively screen the chemical components of JWDZP, which enhanced the screening rate of components with co-elution compounds of low ion intensities and provided a basis for the study of the material foundation of JWDZP.

Objective To investigate the clinical application value of contrast-enhanced chest CT in the detection of responsible vessels for hemoptysis before selective arterial embolization(SAE).Methods The clinical data of 74 patients with hemoptysis trea-ted with interventional therapy and preoperative contrast-enhanced chest CT and digital subtraction angiography(DSA)were ana-lyzed retrospectively.The responsible vessels were identified and then embolized via angiography.The detection of the responsible vessels via preoperative contrast-enhanced chest CT was analyzed.The patients were followed up to observe the efficacy and compli-cations,and the influencing factors of interventional efficacy and recurrence were analyzed.Results A total of 245 responsible ves-sels were detected by preoperative contrast-enhanced chest CT,including bronchial arteries(n=178),ectopic bronchial arteries(n=10)and non-bronchial systemic artery(NBSA)(n=57),which could accurately show the anatomical information of responsible vessels.A total of 4 posterior intercostal arteries were missed.The diagnostic accuracy was 98.4％(245/249).All patients were followed up for 12 to 25.6 months.The immediate hemostasis rate was 93.2％(69/74)and the effective rate was 79.7％(59/74),respectively.The factors affecting the efficacy were bronchial artery to pulmonary circulation fistula,pleural thickening at the bleeding site,and underly-ing lung disease.Among the 59 patients with effective treatment,underlying lung disease was the influencing factor for postoperative recurrence.Conclusion Contrast-enhanced chest CT can provide anatomical information about the responsible vessels for interven-tional therapy of hemoptysis,improving surgical efficiency and reducing the recurrence rate of hemoptysis.

Aim To explore the antimicrobial activity of a novel R-type phage tail-like bacteriocin(PTLB)secreted by Enterobacter cloacae SHAMU191747 a-gainst methicillin-resistant Staphylococcus aureus(MR-SA).Methods Antagonistic activity of E.cloacae SHAMU191747 against MRS A was detected by LB agar plate antagonistic test and LB broth micro-fermentation test.The crude extract of fermentation supernatant of E.cloacae SHAMU191747 was prepared by ultra-high-speed centrifugation and density gradient centrifuga-tion.The novel R-type PTLB in the crude extract was detected by transmission electron microscopy.The an-timicrobial activity of the crude extract against MRSA was verified by LB agar plate spot-seeding method.The molecular weight of the novel R-type PTLB was detected by SDS-PAGE electrophoresis.Results E.cloacae SHAMU191747 secreted a novel R-type PTLB,and had a strong antagonistic effect on MRSA.The no-vel R-type PTLB had a molecular weight of approxi-mately 35 ku and could efficiently kill MRSA.The physical dimensions of its tail-sheath-uncontracted functional molecules were(142.7±4.3)×(13.8±0.6)nm,and those of the tail-sheath-contracted non-functional molecules were(57.7±1.2)×(20.8±1.5)nm.Conclusions The novel R-type PTLB pro-duced by E.cloacae SHAMU191747 can efficiently kill MRSA,and has the potential to be developed into a novel antimicrobial drug with great prospects for clini-cal application.

Objective To compare the contents of alkaloid in Aconiti Kusnezoffii Radix with different degrees of processing and their effects on electrocardiogram and vagus nerve action potential in SD rats;To establish a toxicity evaluation method for Aconiti Kusnezoffii Radix and its processed products.Methods HPLC was used to determine the contents of six alkaloid components,including benzoyl neoaconitine,benzoyl aconitine,benzoyl subeaconitine,neoaconitine,subeaconitine and aconitine in Aconiti Kusnezoffii Radix and Aconiti Kusnezoffii Radix Cocta of soaking and boiled for 30 minutes,boiled for 4 h without soaking,soaking and boiled for 4 h,and soaking and boiled for 8 h.SD rats were subjected to sublingual drainage with Aconiti Kusnezoffii Radix and four types of processed products.The vagus nerve action potential and electrocardiogram of rats before and after administration were recorded,and the correlation analysis between alkaloid content and vagus nerve action potential and heart rate was conducted.Results The contents of alkaloid of the four processed products showed that the content of diester alkaloids was soaking and boiled for 30 min>boiled for 4 h without soaking>soaking and boiled for 4 h>soaking and boiled for 8 h;monoester alkaloid content:boiled for 4 h without soaking>soaking and boiled for 30 min>soaking and boiled for 4 h>soaking and boiled for 8 h.After the administration of each sample,compared with the basal discharge,the vagus nerve discharge of rats with different processed products was changed by sublingual administration,heart rate increased,the degree of arrhythmia increased,and it varied with the degree of processing;the results of correlation analysis showed that there was a significant correlation between the nerve discharge area and the contents of diester alkaloids and total alkaloids.Conclusion The action potential of the vagus nerve and electrocardiogram of rats after sublingual drainage administration can reflect the degree of numbness in the tongue,which can provide reference for the study of tongue sensation of Aconiti Kusnezoffii Radix.

Rapid and accurate detection methods for food-borne pathogens are essential to ensure food safety and human health.One promising innovation in this area is the clustered regularly interspaced short palindromic repeats/CRISPR-associated systems(CRISPR/Cas)biosensor,which utilizes Cas protein and CRISPR RNA(crRNA)ribonucleo protein to specifically recognize target genes,and converts target signals into detectable physical and chemical signals.The CRISPR/Cas biosensor shows many advantages,such as high specificity,programmability,and ease of use,making it promising to pathogen detection.This paper introduced the principles and characteristics of CRISPR/Cas systems,along with the strategies for signal recognition,amplification,and output based on different CRISPR/Cas biosensors,and their respective applications in food-borne pathogen detection.Furthermore,the construction principles and challenges of multiple biosensors based on CRISPR/Cas were explored,as well as their potential for simultaneous detection of multiple pathogens.Finally,the challenges and future development trends of CRISPR/Cas-based biosensors in rapid pathogen detection were discussed,aiming to provide valuable reference and inspiration for biosensor designers and food safety practitioners.

In this work,an electrochemical sensor for detection of Rhodamine B(RhB)was constructed by modifying molecularly imprinted polymer(MIP)and carboxylated multi-walled carbon nanotubes(f-MWCNTs)onto the surface of glassy carbon electrode(GCE).The MIP/f-MWCNT/GCE electrochemical sensor demonstrated outstanding performance in detection of RhB due to the excellent conductivity of f-MWCNT and synergistic selectivity of MIP.Under optimal experimental conditions,the sensor had a wide linear response range(0.01?30 nmol/L,30?500 nmol/L),with limit of detection of 0.01 nmol/L.In addition,the sensor exhibited excellent recognition ability to RhB in the presence of other structurally similar compounds(e.g.,Rhodamine 6G,methylene blue,and methyl orange),and common metal ions(K+,Ca2+,Mg2+and Fe3+).Furthermore,the sensor exhibited good stability and reproducibility.Additionally,the electrochemical sensor exhibited good practical adaptability when analyzing RhB in real samples,with recoveries ranging from 99.8%?105.6%for tap water and 99.2%?105.0%for river water samples.