Cells and exosomes derived from them are extensively used as biological carrier systems. Cells demonstrate superior targeting specificity and prolonged circulation facilitated by their rich array of surface proteins, while exosomes, due to their small size, cross barriers and penetrate tumors efficiently. However, challenges remain, cells' large size restricts tissue penetration, and exosomes have limited targeting accuracy and short circulation times. To address these challenges, we developed a novel concept termed exosomal spheres. This approach involved incorporating platelet-derived exosomes shielded with phosphatidylserine (PS) and linked via pH-sensitive bonds for drug delivery applications. The study demonstrated that, compared with exosomes, the exosomal spheres improved blood circulation through the upregulation of CD47 expression and shielding of phosphatidylserine, thereby minimizing immune clearance. Moreover, the increased expression of P-selectin promoted adhesion to circulating tumor cells, thereby enhancing targeting efficiency. Upon reaching the tumor site, the hydrazone bonds of exosome spheres were protonated in the acidic tumor microenvironment, leading to disintegration into uniform-sized exosomes capable of deeper tumor penetration compared to platelets. These findings suggested that exosome spheres addressed the challenges and offered significant potential for efficient and precise drug delivery.

With the rapid advancement of vaccines, the research and application of vaccine adjuvants have garnered significant attention. Despite the development of numerous vaccine adjuvants, their applications in human vaccines remain limited due to either insufficient efficacy or severe side effects. Consequently, there is growing interest in developing bioactive compounds derived from traditional Chinese medicines (TCMs) as vaccine adjuvants, owing to their natural biocompatibility, diversity, and safety. Here, we systematically review the current application status and potential value of TCM-based bioactive compounds in vaccine adjuvants. Firstly, we elaborate on the types and characteristics of active ingredients, such as polysaccharides, saponins, flavonoids, acids, and alkaloids. The mechanisms by which these compounds function as vaccine adjuvants are then discussed, including their roles in enhancing humoral immunity, cellular immunity, and relieving the immune suppression in the microenvironment. Additionally, we summarize the current strategies for structural modification and platform optimization to adapt to different application scenarios. Finally, we offer insights into the future development directions for these potential adjuvants, highlighting research priorities, technical approaches, and application prospects. In conclusion, natural vaccine adjuvants derived from TCMs present broad application prospects and hold promise for future vaccine development.

To explore the in vitro and in vivo synergistic effect of paclitaxel in combination with co-listin against MDREscherichia coli(E.coli)and the corresponding mechanism of synergism,we measured the MICs of PTX alone and combination of PTX+antimicrobial drugs on E.coli and Staphylococcus aureus(S.aureus)by broth microdilution method.Then,checkerboard method was used to determine the FICI of PTX+COL combination,and the antibacterial synergies of PTX and COL was further explored through analyzing the membrane permeability and efflux pump ac-tivity.The MICs results showed that the MIC values of PTX alone against E.coli(G5,E25)and S.aureus S238 were＞1 024 mg/L and 512 mg/L,respectively.Meanwhile,we found that the anti-bacterial activity of COL against E.coli could be significantly enhanced(MIC decreased by 4 to 8 times)when used in combination with PTX.The checkerboard test showed that the FICI values of PTX combined with COL for E.coli(G5,E25)were 0.31 and 0.29,respectively,indicating a synergistic antibacterial effect on these strains.The FICI values of PTX combined with COL for E.coli G21,S.aureus(S237 and S238)were 0.51,0.75 and 0.53,respectively,indicating additive effects on these strains.In the mouse abdominal infection model,the combination group could ex-tremely significantly reduce the bacterial burden of E.coli in abdominal compared to the COL or PTX alone group(P＜0.001).The analysis of membrane permeability and efflux pump activity showed that PTX combined with COL significantly increased the inner and outer membrane per-meability of E.coli(G5 and E25),and markedly inhibited the efflux pumping activity of E.coli,when compared that of PTX and COL alone(P＜0.01).The above results indicated that the com-bination of PTX and COL could exert a synergistic in vivo and in vitro antibacterial effect on COL-resistant E.coli through increasing bacterial membrane permeability and inhibiting efflux pump activity.This study provides the theoretical foundation for the development of a novel combi-nation regimen for the treatment of MDR E.coli infection.

Generative Artificial Intelligence ishows a broad application prospect in the field of healthcare and has become an important technical means to promote the development of medical informatization.It addresses the multi-faceted challenges of medical record documentation,including efficiency,quality,and doctor-patient communica-tion.It analyzes the adaptability and feasibility of Generative Artificial Intelligence in different clinical scenarios of intelli-gent medical record generation.Additionally,it explores the issues present in current applications and proposes corre-sponding solutions,providing references for the effective application and continuous optimization of Generative Artifi-cial Intelligence in medical record documentation.This provides a theoretical foundation for further expanding the appli-cation scenarios of automatic medical record documentation in China's healthcare industry.

The concept of combined neuro-cardiac imaging emphasizes the systemic interconnection between cerebrovascular and cardiovascular diseases,representing a significant direction in advancement of precision medicine.With superior soft-tissue contrast and multiparametric imaging,MRI provides significant advantages for one-stop,rapid and comprehensive neuro-cardiac evaluation and diagnosis of relative diseases.This consensus systematically outlined the technical specifications for combined neuro-cardiac MRI and proposed strategies for specific patients such as acute ischemic stroke,arrhythmias and renal dysfunction,in order to promote standardized clinical application of MRI led combined neuro-cardiac imaging and enhance precise diagnosis of coexisting cerebrovascular and cardiovascular diseases.

To explore the in vitro and in vivo synergistic effect of paclitaxel in combination with co-listin against MDREscherichia coli(E.coli)and the corresponding mechanism of synergism,we measured the MICs of PTX alone and combination of PTX+antimicrobial drugs on E.coli and Staphylococcus aureus(S.aureus)by broth microdilution method.Then,checkerboard method was used to determine the FICI of PTX+COL combination,and the antibacterial synergies of PTX and COL was further explored through analyzing the membrane permeability and efflux pump ac-tivity.The MICs results showed that the MIC values of PTX alone against E.coli(G5,E25)and S.aureus S238 were＞1 024 mg/L and 512 mg/L,respectively.Meanwhile,we found that the anti-bacterial activity of COL against E.coli could be significantly enhanced(MIC decreased by 4 to 8 times)when used in combination with PTX.The checkerboard test showed that the FICI values of PTX combined with COL for E.coli(G5,E25)were 0.31 and 0.29,respectively,indicating a synergistic antibacterial effect on these strains.The FICI values of PTX combined with COL for E.coli G21,S.aureus(S237 and S238)were 0.51,0.75 and 0.53,respectively,indicating additive effects on these strains.In the mouse abdominal infection model,the combination group could ex-tremely significantly reduce the bacterial burden of E.coli in abdominal compared to the COL or PTX alone group(P＜0.001).The analysis of membrane permeability and efflux pump activity showed that PTX combined with COL significantly increased the inner and outer membrane per-meability of E.coli(G5 and E25),and markedly inhibited the efflux pumping activity of E.coli,when compared that of PTX and COL alone(P＜0.01).The above results indicated that the com-bination of PTX and COL could exert a synergistic in vivo and in vitro antibacterial effect on COL-resistant E.coli through increasing bacterial membrane permeability and inhibiting efflux pump activity.This study provides the theoretical foundation for the development of a novel combi-nation regimen for the treatment of MDR E.coli infection.

Generative Artificial Intelligence ishows a broad application prospect in the field of healthcare and has become an important technical means to promote the development of medical informatization.It addresses the multi-faceted challenges of medical record documentation,including efficiency,quality,and doctor-patient communica-tion.It analyzes the adaptability and feasibility of Generative Artificial Intelligence in different clinical scenarios of intelli-gent medical record generation.Additionally,it explores the issues present in current applications and proposes corre-sponding solutions,providing references for the effective application and continuous optimization of Generative Artifi-cial Intelligence in medical record documentation.This provides a theoretical foundation for further expanding the appli-cation scenarios of automatic medical record documentation in China's healthcare industry.

The concept of combined neuro-cardiac imaging emphasizes the systemic interconnection between cerebrovascular and cardiovascular diseases,representing a significant direction in advancement of precision medicine.With superior soft-tissue contrast and multiparametric imaging,MRI provides significant advantages for one-stop,rapid and comprehensive neuro-cardiac evaluation and diagnosis of relative diseases.This consensus systematically outlined the technical specifications for combined neuro-cardiac MRI and proposed strategies for specific patients such as acute ischemic stroke,arrhythmias and renal dysfunction,in order to promote standardized clinical application of MRI led combined neuro-cardiac imaging and enhance precise diagnosis of coexisting cerebrovascular and cardiovascular diseases.

Objective To explore the optimization for parameters of 5.0T pseudo continuous arterial spin labeling(pCASL)MRI of whole brain.Methods Nine healthy adults were prospectively enrolled,and single-delay pCASL scanning was performed based on a 5.0T MR scanner with 3 sets of labeling gradients:Group A,average gradient(Gavg)=1 mT/m and the ratio of maximum gradient(Gmax)to Gavg(Gratio)=10,group B,Gavg=0.6 mT/m and Gratio=10,group C,Gavg=0.3 mT/m and Gratio=9.The labeling efficiency and cerebral blood flow(CBF)of 3 groups were compared to screen the best labeling gradient group.Results When the marked average blood flow velocity was 40 cm/s,the gradient field tolerance of group C was better than that of group A and B at the situation of reduced B1+and larger B0 offset frequency range.Under the gradient field of group C,the level of labeled artery B1 ranged from 54.19％to 75.36％,with an average of 64.71％.The labeling efficiencies of group C were all ≥85％,and all ≥90％at the average B1 level(64.71％).In the whole gray matter and almost all brain regions,CBF on pCASL under gradient field of group C was significantly higher than that of group A and B(all P＜0.05).Conclusion Low Gavg and low Gmax were the optimal parameters for 5.0T whole brain pCASL MRI.

Objective:To explore the related factors of thrombocytopenia (TCP) occurrence in patients with cirrhosis.Methods:A cross-sectional study was conducted. Inpatients with an initial diagnosis of cirrhosis at Peking University First Hospital from January 1, 2010 to December 31, 2020 were included. Clinical data such as demographic characteristics, etiology of cirrhosis, complications of cirrhosis, laboratory indicators, Child-Pugh grade, invasive procedures, and mortality during hospitalization were collected. A logistic regression model was used to explore the related factors of TCP occurrence in patients with cirrhosis. Categorical variables were compared by the χ2 test. The inter-group comparison was performed using continuous variables, a t-test, one-way analysis of variance (ANOVA), or a nonparametric test. Results:There were a total of 2 592 cases of cirrhosis. 75 cases with incomplete clinical data were excluded. 2 517 cases were included for analysis. The median age was 58 (50, 67) years. Males accounted for 64%. 1 435 cases (57.0%) developed TCP, and 434 cases (17.2%) had grade 3-4 TCP. Gender, primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and concomitant esophagogastric varices (EGV) were the major factors associated with TCP. Females were more prone to combine with TCP ( OR=1.32, 95% CI: 1.12-1.56, P=0.001). Patients combined with EGV ( OR=3.09, 95% CI: 2.63-3.65, P<0.001) were more prone to develop TCP, which was associated with the increased incidence of hypersplenism ( P<0.001). Patients with PBC ( OR=0.64, 95% CI: 0.50-0.82, P<0.001) and PSC ( OR=0.23, 95% CI: 0.06-0.65, P=0.010) were less prone to develop TCP, which was due to the shorter prothrombin time and better coagulation function of PBC patients ( P<0.001), and the lower proportion of hypersplenism in combined PSC patients ( P=0.004). Patients with TCP and grade 3-4 TCP had a higher rate of hemostatic procedures ( P<0.05), but a lower rate of liver biopsy ( P<0.05). Patients with grade 3-4 TCP had a higher nosocomial mortality rate compared to those without ( P=0.004). Conclusion:TCP is common in patients with cirrhosis. However, TCP occurrence is higher in female patients with EGV and lower in patients combined with PBC and PSC. TCP affects invasive procedures and is associated with adverse outcomes.