Probiotics have shown excellent application prospects in preventing and treating many diseases. However, their sensitivity to the harsh environment in vivo always leads to a massive loss of viability and insufficient therapeutic effect. Fortunately, modified probiotics have emerged and provide multiple possibilities for their use in various diseases. Modification not only endows probiotics with extra capacity to resist severe environments but also gives them exogenous characteristics, such as prolonged retention time and improved therapeutic effects. Modified probiotics could combine with other therapies, which has opened up new avenues to enhance the efficacy of probiotic-based therapy. In this review, we have summarized the current physicochemical and biological modification strategies of probiotics. In addition, the progress of research on probiotic-based combination therapy has also been extensively reviewed, which contributes to the enhanced delivery of probiotics or other active constituents and provides new ideas for disease treatment, bioimaging, and diagnosis.

Objective To explore the value of the Physiology and Surgical Severity Score(POSSUM)scoring system in predicting postoperative complications in elderly patients with thoracic surgery,and to ana-lyze its correlation with Clavien-Dindo classification.Methods The data of 182 elderly patients who under-went thoracic surgery in this hospital from October 2019 to March 2023 were retrospectively analyzed.They were divided into the complication group and the non-complication group according to whether there were complications after surgery.The baseline data and POSSUM score of the two groups were analyzed,and the receiver operating characteristic(ROC)curve was drawn to analyze the predictive value of POSSUM for post-operative complications in elderly patients.POSSUM of patients with different Clavien-Dindo classification was compared,and the correlation between POSSUM and Clavien-Dindo classification analyzed.Results The incidence of pulmonary infection was the highest in the complication group,followed by hypoproteinemia.POSSUM in the complication group was higher than that in non-complication group before operation,and the difference was statistically significant(P＜0.05).The ROC curve showed that the area under curve(AUC)value of POSSUM was 0.829;In the complication group,according to Clavien-Dindo classification,there were 5 cases of grade Ⅰ,47 cases of grade Ⅱ,8 cases of grade Ⅱ Ⅲ,7 cases of grade Ⅳ and 8 cases of grade V,the difference was statistically significant(P＜0.05).The correlation analysis showed that POSSUM score was positively correlated with Clavien-Dindo classification(r＞0.513,P＜0.05).Conclusion The POSSUM scoring system has a high value in predicting postoperative complications in elderly patients with thoracic surgery.

Gastric ulcer is a common digestive system disease,and the long-term use of non-steroidal anti-inflammatory drugs(NSAIDs)is the second most important cause.NSAID-induced gastric ulcer animal models are key experimental tools for studying the pathogenesis,corresponding treatment method,and effective mechanisms of NSAID-induced gastrointestinal injury.However,there are currently a lack of reviews on NSAID-induced gastric ulcer animal models.This review summarizes and compares the relevant literature on animal research into indomethacin-and aspirin-induced gastric ulcers in the past 10 years,including the selection of experimental animals,drug solvents,and specific modeling method.The limitations of current models,such as the cumbersome modeling method,incomplete modeling details,inadequate models for clinical use,and lack of comparative drug research,are discussed.Feasible solutions are proposed with the aim of providing an effective reference for research in this field.

Objective:To compare the effects of different reference brain regions on the semi-quantitative SUV ratio (SUVR) of 18F-Florzolotau PET images of Alzheimer′s disease (AD). Methods:The 18F-Florzolotau PET images of 28 (13 males, 15 females, age (57.3±9.5) years) normal controls (NC), 19 patients (4 males, 15 females, age (73.3±7.3) years) with β-amyloid (Aβ)-positive mild cognitive impairment (MCI) and 40 patients (19 males, 21 females, age (61.9±9.1) years) with AD were collected from Huashan Hospital, Fudan University between November 2018 and July 2020. Six semi-quantitative reference brain regions were defined, including whole cerebellum (WC), cerebellar gray matter (GM), cerebellar white matter (WM), parametric estimation of reference signal intensity (PERSI), WC after partial volume correction (WC_pvc), cerebellar GM after partial volume correction (GM_pvc). SUVR was calculated for 14 ROIs, which included the whole brain defined by the automated anatomical labeling (AAL) template, fusiform, inferior temporal, lingual, middle temporal, occipital, parahippocampal, parietal, posterior cingulate, precuneus defined by the AAL template, and Meta ROI composed of the above brain regions, and braak_Ⅰ-Ⅱ, braak_Ⅲ-Ⅳ, braak_Ⅴ-Ⅵ defined by the Desikan Killiany template. AUC was used to evaluate the classification ability of SUVR, and the correlation between SUVR and clinical scale scores were assessed by Spearman rank correlation analysis. Results:The SUVRs of most brain regions showed a steady upward trend in the AD disease spectrum. In the classification task of NC and MCI, the overall performance of SUVR based on WC_pvc was relatively optimal (AUCs: 0.975-1.000). In the classification task of NC and AD, SUVRs of 10 ROIs based on the WC_pvc method showed the relatively best performance (AUCs: 0.976-1.000). The correlation between SUVR of fusiform based on cerebellar WM and mini-mental state examination (MMSE) score was the strongest ( rs=-0.72, P<0.001), and the SUVR of precuneus based on WC_pvc showed the strongest correlation with clinical dementia rating (CDR) score ( rs=0.78, P<0.001). Conclusion:The SUVR based on WC_pvc method performs well in classification and correlation tasks, and is recommended to be used in semi-quantification of 18F-Florzolotau PET images of AD.

Objective:A voxel-level quantification method based on the tau IQ algorithm and Braak staging, excluding β-amyloid (Aβ) imaging, was developed to achieve specific tau quantification. Methods:This cross-sectional study included 92 subjects (35 males, 57 females; age (62.9±10.4) years) from the Nuclear Medicine/PET Center of Huashan Hospital, Fudan University between November 2018 and July 2020. The cohort comprised 28 cognitively normal (CN) individuals, 20 patients with mild cognitive impairment (MCI), and 44 patients with Alzheimer′s disease (AD). All participants underwent 18F-florzolotau PET imaging, Mini-Mental State Examination (MMSE), and Clinical Dementia Rating (CDR) scoring. A longitudinal tau dataset was constructed based on Braak staging. Voxel-level logistic regression fitting provided a baseline matrix, decomposed via least squares to yield the Tau load coefficient. One-way analysis of variance (with post hoc Tukey) was used to compare Tau load and SUV ratio (SUVR) among groups. ROC curve analysis was used to evaluate classification between CN, MCI and AD. Spearman rank correlation was used to assess the relationships between Tau load, SUVR, and MMSE scores or CDR scores. Results:The Tau load in the CN group was close to 0 and significantly lower than that in the MCI and AD groups ( F=55.03, P<0.001; post hoc tests all P<0.001). Significant differences were also observed in the SUVR across all ROIs ( F values: 36.46-55.38, all P<0.001). Compared to SUVR, Tau load demonstrated greater intergroup differences. In ROC curve analyses between each pair of CN, MCI, and AD groups, Tau load consistently achieved the highest AUC (0.754-1.000). Both Tau load and SUVR for each ROI were negatively correlated with MMSE scores ( rs values: from -0.698 to -0.583, all P<0.05) and positively correlated with CDR scores ( rs values: 0.648-0.783, all P<0.05), with Tau load showing the highest absolute correlation coefficients. Conclusion:Compared to the traditional semi-quantitative SUVR method, the Braak-tau IQ algorithm does not require a specific reference brain region to achieve specific tau quantification.

Activating humoral and cellular immunity in lymph nodes (LNs) of nanoparticle-based vaccines is critical to controlling tumors. However, how the physical properties of nanovaccine carriers orchestrate antigen capture, lymphatic delivery, antigen presentation and immune response in LNs is largely unclear. Here, we manufactured gold nanoparticles (AuNPs) with the same size but different shapes (cages, rods, and stars), and loaded tumor antigen as nanovaccines to explore their disparate characters on above four areas. Results revealed that star-shaped AuNPs captured and retained more repetitive antigen epitopes. On lymphatic delivery, both rods and star-shaped nanovaccines mainly drain into the LN follicles region while cage-shaped showed stronger paracortex retention. A surprising finding is that the star-shaped nanovaccines elicited potent humoral immunity, which is mediated by CD4⁺ T helper cell and follicle B cell cooperation significantly preventing tumor growth in the prophylactic study. Interestingly, cage-shaped nanovaccines preferentially presented peptide-MHC I complexes to evoke robust CD8⁺ T cell immunity and showed the strongest therapeutic efficacy when combined with the PD-1 checkpoint inhibitor in established tumor study. These results highlight the importance of nanoparticle shape on antigen delivery and presentation for immune response in LNs, and our findings support the notion that different design strategies are required for prophylactic and therapeutic vaccines.

The typical hallmark of tumor evolution is metabolic dysregulation. In addition to secreting immunoregulatory metabolites, tumor cells and various immune cells display different metabolic pathways and plasticity. Harnessing the metabolic differences to reduce the tumor and immunosuppressive cells while enhancing the activity of positive immunoregulatory cells is a promising strategy. We develop a nanoplatform (CLCeMOF) based on cerium metal-organic framework (CeMOF) by lactate oxidase (LOX) modification and glutaminase inhibitor (CB839) loading. The cascade catalytic reactions induced by CLCeMOF generate reactive oxygen species "storm" to elicit immune responses. Meanwhile, LOX-mediated metabolite lactate exhaustion relieves the immunosuppressive tumor microenvironment, preparing the ground for intracellular regulation. Most noticeably, the immunometabolic checkpoint blockade therapy, as a result of glutamine antagonism, is exploited for overall cell mobilization. It is found that CLCeMOF inhibited glutamine metabolism-dependent cells (tumor cells, immunosuppressive cells, etc.), increased infiltration of dendritic cells, and especially reprogrammed CD8⁺ T lymphocytes with considerable metabolic flexibility toward a highly activated, long-lived, and memory-like phenotype. Such an idea intervenes both metabolite (lactate) and cellular metabolic pathway, which essentially alters overall cell fates toward the desired situation. Collectively, the metabolic intervention strategy is bound to break the evolutionary adaptability of tumors for reinforced immunotherapy.

Objective:To investigate the application effect of the humble tutor mode in the teaching of nursing interns in operating room.Methods:A total of 40 nursing interns in the Operating Room of Affiliated Hospital of Jining Medical University from August 2020 to June 2021 were selected as control group, and 46 nursing interns from August 2021 to September 2022 were selected as experimental group. The interns in the control group received teaching with the conventional tutor mode, and those in the experimental group received teaching with the humble tutor mode. The two groups were compared in terms of the scores of theoretical knowledge and operation skills, voice behavior, self-efficacy, and humble tutor perception. SPSS 19.0 was used to perform the t-test, the chi-square test, and the correlation analysis. Results:At the time of department rotation, the experimental group had significantly higher scores of theoretical knowledge (93.86±3.53) and operation skills (90.90±5.68) than the control group ( P<0.001). Compared with the control group, the experimental group had significantly higher scores of voice behavior [(35.22±7.60) vs. (30.43±5.96), P=0.002], self-efficacy [(28.17±5.03) vs. (24.38±3.39), P<0.001], and humble tutor perception [(37.04±4.34) vs. (26.33±6.63), P<0.001]. Humble tutor perception was positively correlated with voice behavior ( r=0.89, P<0.001), self-efficacy ( r=0.72, P<0.001), operation skills ( r=0.66, P<0.001), and score of theoretical knowledge ( r=0.39, P=0.007). Conclusion:The humble tutor mode has a significant effect in operating room teaching and can improve the assessment scores of theoretical knowledge and operation skills, promote the formation of humble tutors, and strengthen the teaching effect of voice behavior and self-efficacy in nursing interns.

Objective:To explore the effect of perioperative nursing based on enhanced recovery after surgery (ERAS) in patients undergoing off-pump coronary artery bypass (OPCAB) .Methods:From January 2018 to February 2020, 200 OPCAB patients admitted to Affiliated Hospital of Jining Medical University were selected as research subjects using convenience sampling method. The 100 patients admitted from January 2018 to January 2019 served as the control group, while the 100 patients admitted from February 2019 to February 2020 served as the observation group. The control group received routine perioperative nursing, while the observation group received perioperative nursing based on the ERAS. The postoperative ventilator assistance time, Intensive Care Unit (ICU) stay time, anal exhaust time, off-bed time after surgery, and postoperative hospital stay time were compared.Results:The observation group had shorter postoperative ventilator assistance time, ICU stay time, anal exhaust time, off-bed time after surgery, and postoperative hospital stay time compared to the control group, with statistically significant differences ( P<0.05) . Conclusions:Perioperative nursing based on the ERAS can accelerate the postoperative recovery process of OPCAB patients, which is worthy of clinical promotion and practice.

The continuing challenges that limit effectiveness of tumor therapeutic vaccines were high heterogeneity of tumor immunogenicity, low bioactivity of antigens, as well as insufficient lymph nodes (LNs) drainage of antigens and adjuvants. Transportation of in situ neoantigens and adjuvants to LNs may be an effective approach to solve the abovementioned problems. Therefore, an FA-TSL/AuNCs/SV nanoplatform was constructed by integrating simvastatin (SV) adjuvant loaded Au nanocages (AuNCs) as cores (AuNCs/SV) and folic acid modified thermal-sensitive liposomes (FA-TSL) as shells to enhance de novo antitumor immunity. After accumulation in tumor guided by FA, AuNCs mediated photothermal therapy (PTT) induced the release of tumor-derived protein antigens (TDPAs) and the shedding of FA-TSL. Exposed AuNCs/SV soon captured TDPAs to form in situ recombinant vaccine (AuNCs/SV/TDPAs). Subsequently, AuNCs/SV/TDPAs could efficiently transport to draining LNs owing to the hyperthermia induced vasodilation effect and small particle size, achieving co-delivery of antigens and adjuvant for initiation of specific T cell response. In melanoma bearing mice, FA-TSL/AuNCs/SV and laser irradiation effectively ablated primary tumor, against metastatic tumors and induced immunological memory. This approach served a hyperthermia enhanced platform drainage to enable robust personalized cancer vaccination.