The underlying cause of low response rates to existing immunotherapies is that tumor cells dominate tumor immune escape through surface antigen deficiency and inducing tumor immunosuppressive microenvironment (TIME). Here, we proposed an in situ tumor cell engineering strategy to disrupt tumor immune escape at the root by restoring tumor cell MHC-I/tumor-specific antigen complex (MHC-I/TSA) expression to promote T-cell recognition and by silencing tumor cell CD55 to increase the ICOSL⁺ B-cell proportion and reverse the TIME. A doxorubicin (DOX) and dual-gene plasmid (MAC pDNA, encoding both MHC-I/ASMTNMELM and CD55-shRNA) coloaded drug delivery system (LCPN@ACD) with tumor targeting and charge/size dual-conversion properties was prepared. LCPN@ACD-induced ICD promoted DC maturation and enhanced T-cell activation and infiltration. LCPN@ACD enabled effective expression of MHC-I/TSA on tumor cells, increasing the ability of tumor cell recognition and killing. LCPN@ACD downregulated tumor cell CD55 expression, increased the proportion of ICOSL⁺ B cells and CTLs, and reversed the TIME, thus greatly improving the efficacy of αPD-1 and CAR-T therapies. The application of this in situ tumor cell engineering strategy eliminated the source of tumor immune escape, providing new ideas for solving the challenges of clinical immunotherapy.

Transarterial radioembolization (TARE) is a widely utilized therapeutic approach for hepatocellular carcinoma (HCC), however, the clinical implementation is constrained by the stringent preparation conditions of radioembolization agents. Herein, we incorporated the superstable homogeneous iodinated formulation technology (SHIFT), simultaneously utilizing an enhanced solvent form in a carbon dioxide supercritical fluid environment, to encapsulate radionuclides (such as ¹³¹I,¹⁷⁷Lu, or ¹⁸F) with lipiodol for the preparation of radiolipiodol. The resulting radiolipiodol exhibited exceptional stability and ultra-high labeling efficiency (≥99%) and displayed notable intratumoral radionuclide retention and in vivo stability more than 2 weeks following locoregional injection in subcutaneous tumors in mice and orthotopic liver tumors in rats and rabbits. Given these encouraging findings, ¹⁸F was authorized as a radiotracer in radiolipiodol for clinical trials in HCC patients, and showed a favorable tumor accumulation, with a tumor-to-liver uptake ratio of ≥50 and minimal radionuclide leakage, confirming the feasibility of SHIFT for TARE applications. In the context of transforming from preclinical to clinical screening, the preparation of radiolipiodol by SHIFT represents an innovative physical strategy for radionuclide encapsulation. Hence, this work offers a reliable and efficient approach for TARE in HCC, showing considerable promise for clinical application (ChiCTR2400087731).

Objective To observe the effects of Huatan Quyu Decoction on cognitive function and the expressions of GABA and VILIP-1 in brain tissue of rats with cerebral small vessel disease;To discuss its mechanism for treatment on cerebral small vessel disease.Methods Totally 48 male SD rats were randomly divided into blank group,model group,Huatan Quyu Decoction low-and high-dosage groups,with 12 rats in each group.Except for the blank group,a rat model of cerebral small vessel disease was prepared by in vitro injection of homologous microemboli.Huatan Quyu Decoction low-and high-dosage groups were given Huatan Quyu Decoction 1.25 and 2.5 g/kg by gavage,the blank group and model group were gavage with equal amounts of distilled water for 28 consecutive days.Morris water maze experiment was conducted on day 1,7,14,and 28 after administration to evaluate the learning and memory abilities of rats,HE staining was used to observe pathological changes in hippocampal tissue,and immunohistochemical staining was used to detect the expressions of GABA and VILIP-1 proteins in brain tissue.Results Compared with the blank group,the escape latency of Morris water maze experiment in model group significantly prolonged(P<0.05),and the number of crossing platforms was significantly reduced(P<0.05);the arrangement of hippocampal tissue cells was disordered,gaps widen,and nuclei atrophy and necrosis,the GABA expression in brain tissue significantly decreased(P<0.05),while the VILIP-1 expression significantly increased(P<0.05).Compared with the model group,the escape latency of Morris water maze experiment in the Huatan Quyu Decoction low-and high-dosage groups significantly shortened(P<0.05)on day 7,14,and 28 of administration,and the number of crossing platforms significantly increased(P<0.05),GABA expression significantly increased(P<0.05),while VILIP-1 expression significantly decreased(P<0.05).Compared with the Huatan Quyu Decoction low-dosage group,the escape latency of Morris water maze experiment in Huatan Quyu Decoction high-dosage group decreased at various time points,and the number of crossing platforms increase,the pathological damage of hippocampal tissue was reduced,the expression of GABA in brain tissue increased,and the expression of VILIP-1 decreased,with statistical significance(P<0.05).Conclusion Huatan Quyu Decoction can increase the expression of GABA in brain tissue and inhibit the expression of VILIP-1,thereby improve the cognitive function of rats with cerebrovascular disease.

OBJECTIVE To analyze the influential factors on trough concentration （cmin） and area under the drug concentration time curve （AUC） of voriconazole （VRZ） in pediatric patients with thalassemia undergoing hematopoietic stem cell transplantation （HSCT）. METHODS A total of 60 pediatric patients with thalassemia undergoing HSCT who used VRZ for prevention or treatment of invasive fungal infection were collected in our hospital from January 2021 to January 2024. The plasma concentration of VRZ was measured by high-performance liquid chromatography and the AUC was calculated. The factors affecting cmin and AUC of VRZ were analyzed using multiple linear regression. RESULTS A total of 120 cases of VRZ cmin in 60 pediatric patients was obtained and 27 cases of VRZ AUC in 26 pediatric patients were obtained. The median concentration of VRZ cmin was 0.31 mg/L； 46 cases had a cmin in 0.5-5 mg/L（ 38.33%）， 2 cases had a cmin＞5 mg/L（ 1.67%）， and 72 cases had a cmin＜0.5 mg/L. The median AUC of VRZ was 11.68 mg·h/L. The patient’s body weight， HSCT postoperative days， lymphocyte count， and combined use of phenytoin sodium， tacrolimus or cyclosporine had significant effects on VRZ cmin （P＜0.05）. Lymphocyte count and combined use of phenytoin sodium had significant effects on VRZ AUC （P＜0.05）. CONCLUSIONS The body weight， HSCT postoperative days， lymphocyte count， and combined use of phenytoin sodium， tacrolimus or cyclosporine are independent factors affecting VRZ cmin. Lymphocyte count and combined use of phenytoin sodium are independent factors affecting VRZ AUC.

OBJECTIVE To investigate the mechanism by which Ginkgo flavone aglycone （GA） reduces the cardiotoxicity of doxorubicin （DOX） based on transcriptomics and proteomics. METHODS Thirty-six mice were randomly assigned to control group （CON group， tail vein injection of equal volume of physiological saline every other day+daily intragastric administration of an equal volume of physiological saline）， DOX group （tail vein injection of 3 mg/kg DOX every other day）， and GDOX group （daily intragastric administration of 100 mg/kg GA+tail vein injection of 3 mg/kg DOX every other day）， with 12 mice in each group. The administration of drugs/physiological saline was continued for 15 days. Mouse heart tissues were collected for RNA-Seq transcriptomic sequencing and 4D-Label-free quantitative proteomic analysis to screen differentially expressed genes and proteins， which were then subjected to Kyoto encyclopedia of genes and genomes （KEGG） enrichment analysis. The expression levels of Apelin peptide （Apelin）， phosphatidylinositol 3-kinase （PI3K）， and protein kinase B （Akt） mRNA and protein in mouse heart tissues， as well as the phosphorylation levels of PI3K and Akt proteins， were verified. H9c2 cardiomyocytes were divided into control group （CON group）， DOX group （2 μmol/L）， and GDOX group （2 μg/mL GA+2 μmol/L DOX） to determine cell viability and the levels of key glycolytic substances in the cells. RESULTS Six common pathways were identified from transcriptomics and proteomics， including the Apelin signaling pathway， the PI3K-Akt signaling pathway， and insulin resistance. Among them， the Apelin and PI3K-Akt signaling pathways were the most enriched in terms of gene numbers. Target validation experiments showed that compared to the CON group， the relative expression of Apelin， PI3K and Akt mRNA and protein levels， as well as the phosphorylation levels of PI3K and Akt proteins， were significantly decreased in the DOX group （P＜0.05 or P＜0.01）. The relative expression of Apelin， PI3K and Akt mRNA and the phosphorylation levels of PI3K and Akt proteins were significantly increased in the GDOX group as compared with the DOX group （P＜0.05 or P＜0.01）. Cellular experiments indicated that compared to the CON group， cell viability in the DOX group was significantly decreased （P＜0.05）， the relative uptake of glucose and the relative production of pyruvate and lactate were significantly increased （P＜0.05）， and the relative production of ATP was significantly reduced （P＜0.05）. Compared to the DOX group， cell viability in the GDOX group was significantly increased （P＜ 0.05）， and the relative production of pyruvate and lactate was significantly reduced （P＜0.05）. CONCLUSIONS GA may alleviate DOX-induced cardiotoxicity by upregulating the mRNA and protein expression of Apelin， PI3K， and Akt in heart tissues， and regulating glycolytic processes.

Ischemic stroke has a high rate of disability and mortality and is often accompanied by white matter injury(WMI).WMI patients often have cognitive disorders,emotional disorders,sensorimotor disorders,urinary incontinence and other symptoms,which seriously affect daily life.WMI can be detected early through imaging techniques,but there is a lack of appropriate intervention and specific treatment.Studying the pathological mechanism of WMI after ischemic stroke is helpful to prevent the occurrence of WMI,delay its progression,and contribute to the development of effective drugs or specific treatments.This article reviewed the research progress of WMI mechanism after ischemic stroke in order to provide scientific basis for clinical prevention and treatment.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective The metabolites of tolvaptan in rats were identified by ultra-performance liquid chromatography-quadrupole-exactive orbitrap high-resolution mass spectrometry(UFLC-Q-Exactive Orbitrap MS),and the possible metabolic pathways of tolvaptan in rats were discussed.Methods Plasma,urine and fecal samples from rats were collected after a single oral administration of 60 mg·kg-1 tolvaptan solid dispersion solution.The protein in the samples was precipitated with acetonitrile.UFLC-Q-exactive orbitrap MS technology was adopted for the sample analysis and the data were processed by Xcalibur 2.0 software.Results According to the retention time,precise relative molecular mass,characteristic fragment ions and related literature reports of each compound,35 metabolites were identified in rat biological samples.Moreover,23,26 and 30 metabolites in the plasma,urine and feces were identified,respectively.The major metabolic pathways of tolvaptan were identified as hydroxylation,carboxylation,hydrolysis,dehydrogenation,glucuronidation and acetylation.Conclusion Our study confirmed the major metabolites of tolvaptan in rats,enriched the metabolite spectrum of tolvaptan in vivo,and provided an experimental basis for the in-depth study of the pharmacodynamic substance basis of tolvaptan.

【Objective】 To analyze the characteristics and mobility of the overlapping population of voluntary blood donation and plasmapheresis donation, so as to provide a scientific basis for the formulation of recruitment and retention strategies for blood donation and plasmapheresis donation, and to further propose a scientific reference for the decision-making of blood banks and plasmapheresis station management in China. 【Methods】 The basic information of blood donors and plasmapheresis donors in two counties in Guangyuan, Sichuan Province, which carried out whole blood collection and plasmapheresis collection from the establishment of the station to July 31, 2021 was statistically compared and analzed using the chi-square test and Post hoc testing test. 【Results】 As of July 31, 2021, a total of 50 658 people participated in blood donation and 63 375 people participated in plasmapheresis donation in Jiange County and Cangxi County, with a total overlap of 6 189 people. In the two regions, 16 458 (35.2%) people aged 40 to 50, and 35 558 people (56.1%) were over 50 years old. Among the overlapping population, 2 496 (40.3%) were 40 to 50 years old, accounted for the largest proportion, and 3 146 (50.8%) were males. Significant differences were noticed in age (P<0.001) and gender (P<0.001). There was a shift in dontion in 5 183, including 2 072 people from plasma to blood and 3 111 people from blood to plasma, among which 2 671 (51.5%) were men and 3 632 (70.1%) were over 50 years old, with significant differences in gender (P<0.05) and age (P<0.001). 【Conclusion】 There were a small number of donors donating both blood and plasma in Jiange and Cangxi, and men aged 40 to 50 were the majority, and people over 50 years old were more likely to shift the donation goals. The vast majority of donors have a single and fixed donation goal (blood or plasma), and are not easy to change.

【Objective】 To analyze the dynamic relationship between the setting up of plasmapheresis station and the volume of voluntary blood donation collected using panel vector autoregressive model, so as to provide scientific reference for the management policies of blood stations and plasmapheresis stations in China. 【Methods】 The data collected from blood stations in seven administrative regions of Guangyuan, Sichuan Province from 2011 to 2021, as well as plasma collection data from two plasmapheresis stations in the region within two years since their operation, were collected. A panel vector autoregressive model was constructed. Impulse response analysis and variance decomposition analysis were used to analyze the impact and time lag effects of simulated plasmapheresis station settings on the collection volume of voluntary blood donation. Covariance analysis was used to explore whether the establishment of plasmapheresis station had an impact on the volume of voluntary blood donation collected after excluding the impact of initial value differences. 【Results】 The pulse response results showed that after the plasmapheresis station was set up, there was a negative impact effect on the voluntary blood donation collection volume at the first stage, and its impact began to rise after the second stage, reached the highest value in the third stage, and then began to decline. After the seventh stage, it tended to be stable. However, within the 10 stage range, the confidence interval for the response strength of voluntary blood donation collection volume always included 0, indicating that the response of blood collection volume to the plasmapheresis station setting in the region was not statistically significant. The results of variance decomposition showed that the contribution of collection volume of voluntary blood donation to their own impact reached 94.3%. In terms of the contribution of plasmapheresis station factors, the number of plasma donors has a relatively greater impact on the volume of voluntary blood donation collected(2.2%). Covariance analysis showed that after removing the initial confounding factors, whether to establish a plasmapheresis station had no significant impact on blood donation volume in the two groups of regions (P>0.05). 【Conclusion】 The establishment of a new plasmapheresis station will have a certain impact on blood collection volume of blood stations in the region in a short term, but in the long term, it may not directly affect the voluntary blood donation collection in the region.