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.

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.

Objective Aiming to develop a distance-adaptive visual function self-examination system based on tablet computers and evaluate its accuracy.Methods Utilizing ArUco technology on a tablet device equipped with the camera,a system was developed to assess visual functions by identifying QR codes within a 2-meters range for real-time ranging.This system integrates various visual function tests,including visual acuity test(conventional visual acuity test and high-pass visual acuity test with varying contrasts),accommodative amplitude test,and visual field test at the foveal(5°).A total of 22 healthy subjects(44 eyes)participated in visual function assessments,with 6 subjects undergoing visual acuity tests at varying distances(1 m,1.25 m,1.6 m,2 m)and accommodative amplitude tests under both refractive correction and simulated undercorrection of-3.00D.The program distance and actual distance were compared,the consistency of visual acuity outcomes for identical optotype at different distances were assessed,the accommodative amplitude under refractive correction and undercorrection were analyzed,the repeatability of accommodative amplitude outcomes was evaluated using Intraclass Correlation Coefficient(ICC),and the contrast threshold and efficacy of visual field test outcomes were analyzed.Results The program distance and actual distance showed good agreement.High-pass visual acuity tests with the same contrast showed no significant differences at different distances(P?>?0.05),while conventional visual acuity tests showed significant differences at distances of 0.9 to 1.1 meters compared to other distances(P?

【Objective】 To explore the application effect of target management combined with intelligent display system on apheresis platelet donor recruitment. 【Methods】 Control group: 317 apheresis platelet donors were recruited according to the conventional appointment mode of intelligent display system from October 2020 to March 2021, with a total of 1 073 donations. Experimental group: 404 apheresis platelet donors were recruited using quantitative target management plus the intelligent display system from April 2021 to September 2021, with a total of 1 308 donations. The number of first-time donors, repeated donors, recalled donors after first-time donation, and their corresponding donations, as well as the double-dose collection rate, and the transfer-in/-out of platelet product were analyzed and compared. 【Results】 The number of first-time donors increased from 89 (28.08%) to 179 (44.31%) while repeated donors decreased from 228 (71.92%) to 225 (55.69%), all P<0.05. The number of recalled donors after first-time donation increased from 42 (45.19%) to 82 (47.81%), P>0.05.The cumulative number of first-time and repeated platelet donors increased from 149 (13.89%) to 331 (25.31%), and 924 (86.11%) to 977 (74.69%), respectively(all P<0.05). The recalled donors after first-time donation increased from 60 (40.26%) to 152 (45.92%)(P>0.05). The double-dose collection rate decreased from 24.70% (265/1 073) to 13.46% (176/1 308)(P<0.05). The proportion of transfer-in platelets decreased from 3.64% (48/1 317) to 1.52% (22/1 452), while transfer-out platelet increased from 0.23% (3/1 317) to 2.34% (34/1 452)(all P<0.05). 【Conclusion】 The intelligent display system is conducive to facilitate the development of platelet donor recruitment and ensure the clinical supply of apheresis platelets.

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterized by the infiltration of bone and multiple organs by foamy lipid-laden histiocytes. ECD is easy to be misdiagnosed due to its complicated clinical manifestations. We report a patient who visited the hospital due to hypothalamic dysfunction, with central nervous system, pancreas, and lower limb bones involvements. Together with the evidence of clinical manifestations, imaging and pathology, this patient was diagnosed with ECD. After treatment with interferon-α, both the clinical symptoms and imaging manifestations of this patient were significantly improved.

Objective:To evaluate the clinical value of the transcutaneous neuromodulation (TN) in improving gastrointestinal function after gastrointestinal tumor operation.Methods:From April 2019 to June 2020, at The Affiliated People′s Hospital of Ningbo University, 100 patients who underwent gastrointestinal tumor surgery were included. The 100 patients were randomly divided into treatment group(receiving TN treatment, 50 cases)and control group (receiving sham TN treatment, 50 cases). The clinical data of the two groups was compared to evaluate the recovery of gastrointestinal function, which included the time of first defecation, time of first flatus, time of first ambulation, time of resuming diet, the incidence of nausea and vomiting within 3 d after operation and pain score (0 to 10). Heart rate variability (HRV) was compared between two groups to analyze the possible mechanism of TN improving gastrointestinal function after gastrointestinal tumor surgery. Independent sample t test and Chi-square test were used for statistical analysis. Results:Among 100 patients, there were 63 male and 37 female patients, the age was (67.0±11.3) years old, ranged from 28 to 92 years old. Compared with the control group, the time of first defecation, first flatus, first ambulation and resuming diet of treatment group reduced by 31.0%, 39.8%, 38.0% and 32.4% ((72.1±3.0) h vs.(104.5±2.9) h, (49.4±5.7) h vs.(82.1±3.1) h, (3.1±0.7) d vs.(5.0±0.9) d, (4.8±0.9) d vs. (7.1±0.8) d)), respectively; the pain scores on the day 2 and day 3 after operation and incidence of nausea and vomiting within 3 d after operation decreased by 50.0%, 65.5%, 26.0%(1.5±0.6 vs. 3.0±0.7, 1.0±0.6 vs. 2.9±0.6, 16.0%, 8/50 vs. 42.0%, 21/50), respectively, and the differences were statistically significant ( t=54.28, 35.72, 11.67, 13.66, 12.00 and 14.90, χ2=8.21, all P<0.01). The results of HRV analysis showed that the high frequency on day 3 was higher than that on day 1 of treatment group, and the ratio of low frequency to high frequency after operation was lower than that before operation of treatment group (0.5±0.1 vs. 0.4±0.1, 1.2±0.7 vs. 1.9±1.0), and the differences were statistically significant( t=-4.81 and 4.26, both P<0.01), which indicated TN could enhance vagal activity. Conclusions:TN promote the recovery of gastrointestinal function after gastrointestinal tumor operation, and can be used as an adjuvant therapy to accelerate the recovery of gastrointestinal function after gastrointestinal tumor operation.

Objective:To study the risk factors and microbial spectrum for infectious complications for patients with biliary tract cancer after major hepatectomy with cholangiojejunostomy.Methods:Enrolled into this study were 78 consecutive patients (57 patients with perihilar cholangiocarcinoma, 17 with intrahepatic cholangiocarcinoma and 4 with gallbladder cancer), who underwent major hepatectomy with cholangiojejunostomy at Nanjing Drum Tower Hospital between September 2010 and March 2019. The clinical data were reviewed using multivariate analysis to find independent risk factors for postoperative infectious complications. Microorganisms isolated from bile and infected sites were determined to study the microbial spectrum.Results:A total of 45(57.7%) patients suffered from postoperative infectious complications. Male sex ( OR=7.765, 95% CI=1.895-31.815, P<0.05) was the independent risk factor, whereas increased preope-rative red blood cell (RBC) ( OR=0.151, 95% CI=0.038-0.592, optimal cut-off value=3.7×10 12/L) and increased total cholesterol (TC) on postoperative day (POD) 1 ( OR=0.227, 95% CI=0.083-0.626, optimal cut-off value=3.5 mmol/L) were protective factors (both P<0.05). The area under the receiver operating characteristic (ROC) curve was 0.805 (95% CI=0.707-0.902, P<0.05). 205 and 230 microorganisms were cultured respectively from 286 and 681 specimens which were collected from pre-/intraoperative bile and potentially infected sites. Staphylococcus, enterococcus, acinetobacter, klebsiella and pseudomonas were the most common pathogens on bile culture. The first 5 most frequently isolated microorganisms from the infected sites were enterococcus, staphylococcus, klebsiella, candida and xanthomonas. Sixteen (61.5%) of 26 patients had at least one pathogen being isolated from the infected sites with the pathogen being previously isolated in bile culture. Conclusions:Male sex were independent risk factors of infectious complications. Increased preoperative RBC and inreased TC on POD were proteetive factors. For patients without a positive bile culture, a third-generation cephalosporin can be considered as a prophylactic antibiotic. It is important to identify high-risk patients and monitor perioperative pathogens actively to prevent and to cure postoperative infectious complications.

Objective:To investigate the mechanisms of effects of high fat and high fructose diet on rat aging.Methods:Adult male SD rats were divided into normal diet(ND) group and high fat and high fructose diet(HFHFD) group. After treatment for 48 weeks, these rats were sacrificed and the blood, liver, and brain tissues were collected. Serum triglyceride(TG), total cholesterol(TC), low density lipoprotein-cholesterol(LDL-C), high density lipoprotein-cholesterol(HDL-C) levels were determined by automatic biochemical analyzer. The serum levels of interluekin-2(IL-2), IL-6, and advanced glycation end products(AGEs) were measured using enzyme linked immunosorbent assay. The expressions of p16, p21, and p53 genes in the liver and brain tissues were detected by real-time quantitative PCR and western blot.Results:After 48 weeks treatment, there were significant differences in body weight and fasting plasma glucose between two groups. Serum TG, TC, and LDL-C in HFHFD group were significantly higher than those in the ND group( P<0.05), with an increase trend in HDL-C but without statistical difference. Compared with ND group, the level of IL-2 in HFHFD group was significantly decreased while the levels of IL-6 and AGEs were significantly increased(all P<0.05). The levels of p16 and p21 mRNA expressions as well as p53 and p21 protein expressions in liver and brain in HFHFD group were markedly increased compared with ND group(all P<0.05). Conclusion:Long-term high fat and high fructose diets accelerate the aging process of rats, which may be related to the damage of the immune system and the changes of cell senescence related gene expressions in liver and brain tissues.