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 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 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 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 investigate the influencing factors for pancreatic endocrine and exocrine insufficiency after pancreaticoduodenectomy.Methods:The retrospective case-control study was conducted. The clinicopathological data of 168 patients who underwent pancreaticoduodenectomy in the Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from January 2016 to December 2017 were collected. There were 96 males and 72 females, aged (64±13)years, with a range from 38 to 75 years. Of the 168 patients, 36 had pancreatic endocrine insufficiency while 8 had pancreatic exocrine insufficiency preoperatively. All patients underwent pancreaticoduodenectomy. Observation indications: (1) surgical situations and follow-up; (2) analysis of influencing factors for pancreatic endocrine insufficiency after pancreaticoduodenectomy; (3) analysis of influencing factors for pancreatic exocrine insufficiency after pancreaticoduodenectomy. Follow-up using out-patient examination and telephone interview was performed to detect postoperative condition of blood glucose control, diet and nutrition, tumor recurrence and metastasis up to June 2018. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the independent sample t test. Measurement data with skewed distribution were described as M (range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Univariate analysis was conducted using the chi-square test. Multivariate analysis was conducted using the Logistic regression model. Results:(1) Surgical situations and follow-up: all the 168 patients underwent pancreaticoduodenectomy successfully and recovered well after operation. All patients were followed up for 6 months. The level of fasting and postprandial blood glucose of the 168 patients after surgery were 7 mmol/L(range, 5-9 mmol/L) and 10 mmol/L(range, 7-14 mmol/L), respectively. The defecation frequency was (2.4±1.2)times per day. No tumor recurrence or metastasis occurred in either patient. One hundred and thirty-two of the 168 patients were included in the study excepting patients with pancreatic endocrine insufficiency before operation. At postoperative 6 months, 47 patients developed pancreatic endocrine insufficiency, with an incidence of 35.61%(47/132). One hundred and sixty of the 168 patients were included in the study excepting patients with pancreatic exocrine insufficiency before operation. At postoperative 6 months, 68 patients had pancreatic exocrine insufficiency, with an incidence rate of 42.50%(68/160). (2) Analysis of influencing factors for pancreatic endocrine insufficiency after pancreaticoduodenectomy. Results of univariate analysis showed that gender, metabolic syndrome, chronic pancreatitis, excision point, and postoperative chemotherapy were the related factors for pancreatic endocrine insufficiency after pancreaticoduodenectomy ( χ2=5.300, 6.270, 4.473, 4.392, 5.397, P<0.05). Results of multivariate analysis revealed that male and metabolic syndrome were independent risk factors for pancreatic endocrine insufficiency after pancreaticoduodenectomy [ hazard ratio ( HR)=5.252, 5.364, 95% confidence interval ( CI): 1.362-6.382, 1.891-12.592, P<0.05)]. (3) Analysis of risk factors for pancreatic exocrine insufficiency after pancreaticoduodenectomy. Results of univariate analysis showed that body mass index (BMI), chronic pancreatitis, total bilirubin, excision point, postoperative pancreatic fistula as grade B or C, and pancreatic fibrosis were related factors for pancreatic exocrine insufficiency after pancreaticoduodenectomy ( χ2=1.691, 4.910, 7.763, 5.605, 4.663, 7.700, P<0.05). Results of multivariate analysis showed that BMI<18.5 kg/m 2, chronic pancreatitis, total bilirubin ≥171 μmol/L were independent risk factors for pancreatic exocrine insufficiency after pancreaticoduodenectomy ( HR=3.695, 5.231, 7.623, 95% CI: 1.232-7.324, 2.161-6.893, 1.562-5.235, P<0.05). Conclusions:Male and metabolic syndrome are risk factors for pancreatic endocrine insufficiency after pancreaticoduodenectomy. BMI<18.5 kg/m 2, chronic pancreatitis, and total bilirubin ≥171 μmol/L are risk factors for pancreatic exocrine insufficiency after pancreaticoduodenectomy.

Objective: To investigate the clinical features, diagnosis, occurrence sequence and clonal origin of chronic lymphocytic leukemia complicated with multiple myeloma. Methods: The diagnosis and treatment of one patient with multiple myeloma and chronic lymphocytic leukemia who was admitted to the First Hospital of Jilin University in May 2018 was retrospectively analyzed, and the related literatures were reviewed. Results: This patient began with lumbosacral pain, and he was diagnosed as chronic lymphocytic leukemia complicated with multiple myeloma after bone marrow aspiration, flow cytometry, and blood and urine immunofixation electrophoresis. It is recommended that Rd (lenalidomide + dexamethasone) or MPV (melphalan + prednisone + bortezomib) regimen, but the patient did not receive chemotherapy and died of infectious diarrhea 1 month later. Conclusions The occurrence of multiple myeloma and chronic lymphoblastic leukemia may originate from the same clone or different new clone. It is very rare that multiple myeloma and chronic lymphoblastic leukemia can co-occur. Therapeutic options tend to be more aggressive multiple myeloma-based regimen.