In the earliest days,the idea that surviving a single infection often resulted in lifelong immunity to the infecting pathogen was recorded and then led to the discovery of vaccination.We have now confirmed that such protection is primarily based on the generation of immunological memory in antibody response.With the wide implementation of more and more vaccines around the world,it is well documented that different vaccines have different potential regarding to the duration of antibody response.In clinical observations,live-attenuated vaccines often elicit long-term immunity but are also accompanied with risks in safety that are hard to avoid.In order to develop novel vaccines with both excellent potential in eliciting antibody memory and low safety risk,it is critical to further investigate the mechanism of antibody memory in the perspective of immunology.Antibody memory is mediated by certain long-lived B cells:long-lived plasma cell can secret antibody to maintain serum antibody titer while memory B cell contributes to the rapid immune response during the secondary encounter of pathogens.Cellular and molecular processes that drive the production of long-lived plasma cells and memory B cells are subjects of intensive research and have important implications for global health.Several factors in the vaccine would indeed affect and regulate these processes,including the antigen valency,vaccine kinetics and the signal integration of both antigen and danger molecules.Many studies have focused on strategies to manipulate these factors to improve or develop new vaccines.Here,we will summarize our current knowledge on how the component in vaccines will affect their potential in generating and sustaining antibody memory,and also point out the challenges we face in the route of developing a"perfect"vaccine.

Objective To create a mouse model of colorectal polyps with Apc-Kras-Cre gene mutations using the tamoxifen induction method.Methods Mice with Apc-Kras-Cre mutations were divided into four groups and injected intraperitoneally with different concentrations and dosages of tamoxifen for different durations,with group 1 injected with low dosage tamoxifen(5 mg/kg)for 1 day,group 2 injected with low dosage tamoxifen(5 mg/kg)for 3 days,group 3 injected with high dosage tamoxifen(50 mg/kg)for 1 day,group 4 injected with high dosage tamoxifen(50 mg/kg)for 3 days.C57BL/6J mice were used as a healthy control group and survival and changes in body weight were observed.All mice were euthanized 4 weeks post-tamoxifen induction and the colon length and number and size of intestinal polyps were observed.Histological changes in the intestinal tissue and polyps were detected by hematoxylin and eosin staining.Results The survival rate of male mice was higher(P＜0.001)and the morbidity rate of male mice was lower compared with female mice(P＜0.05).The survival rate differed significantly among the four groups(P＜0.01).All groups showed significant changes in body weight compared with the healthy control group(P＜0.001).There were also significant differences in weight changes between tamoxifen-induced groups 1 and 2,between groups 2 and 3,and between groups 1 and 4(P＜0.001,P＜0.01,P＜0.05,respectively).There were no significant differences in colon length between any treated group and the healthy control group(P＞0.05),but colon length did differ between tamoxifen-induced groups 1 and 3(P＜0.05).Polyp size varied in each group of tamoxifen-treated mice,with most polyps occuring at the distal end of the colon,while mice in groups 3 and 4 had more and larger polyps.Histopathological examination showed intestinal polyps with uneven and misaligned glandular and epithelial arrangements,a loosely-packed intestinal mucosal barrier,and irregularly-distributed crypts in tamoxifen-induced mice compared with the healthy control group,while mice in tamoxifen-induced groups 3 and 4 showed signs of inflammation and mice in group 4 showed necrosis of cells in some regions.Conclusions Tamoxifen-induced Apc-Kras-Cre model mice were successfully established,with the group 3 induction method being the most suitable.

Radix Bupleuri has been used in traditional Chinese medicine for over 2000 years with functions of relieving exterior syndrome,clearing heat,regulating liver-qi,and lifting yang-qi.Its medicinal properties have been widely used in Eurasia and North Africa.As the main bioactive compounds in Radix Bupleuri,saikosaponins(especially saikosaponin A and saikosaponin D)have anti-inflammatory,anti-tumor,antioxidant,antivirus,immune regulatory,and liver protective effects.This article reviews the pharmacological activity,mechanism of action,and current applica-tion status of saikosaponins,in order to provide new insights for further research and development of Radix Bupleuri.

Streptococcus parasuis(S.parasuis)is a close relative of S.suis and can cause meningi-tis,pneumonia or systemic symptoms in affected animals.In this paper,the dominant strain was i-solated from diseased pigs with pneumonia in Jilin,China,and the isolated strain was identified as S.parasuis by 16S rRNA,it was named WYF-8B.Resistance was tested by the susceptibility tablet diffusion method,and WYF-8B was resistant to bacitracin,sulfamethoxoprim,lincomycin,erythro-mycin,fosfamycin,azithromycin,penicillin,doxycycline,cotrimotrixazole,sulfamisoxazole,cipro-floxacin,enrofloxacin,tetracycline,benzoxacillin,gentamicin,efazolin,and ampicillin.It was highly sensitive to florfenicol,chloramphenicol.Iochemical identification revealed that WYF-8B could fer-ment salicylic acid,maltose,lactose,sucrose,oxaesin,and glucose;nonfermentable mannitol,urea,raffinose,xylose,arabinose,and sorbitol.Using the second-generation whole-genome sequencing technology to study the WYF-8B resistant genotype,it was found that it carried the macrolide anti-biotic resistance genes Mef(E)and ErmB;resistance genes pbp2b,pbp1a,and pbp2x to β-lactam antibiotics;resistance genes gyrA,parC,and grlB to fluoroquinolones;resistance genes ANT(6)-Ia,AAC(6')-Ie-APH(2')-Ia,ANT(9)-Ia,APH(3')-Ⅲa to aminoglycoside antibiotics;re-sistance groups lnuB,lmrC,lmrD against lincomide antibiotics;resistance gene tetM to tetracy-cline antibiotics;the resistance gene of bacitracin,bcrA.The results found that the resistance phe-notype matches the resistance genotype of the sequencing results.The study of WYF-8B virulence factors found that WYF-8B carried 13 virulence factors(pavA,fbp 54,clpP,cps 4,cps 4 I,wbtB,cps,sI,tufA,galE,hasC,groEL,wrbtL,wbbtF),which mainly acted to promote bacterial diffu-sion,transfer,settlement,antiphagocytosis and immune evasion.The results of drug sensitivity test provide a reference for the study of clinical medication of S.parasuis,and drug resistance pheno-type and virulence factors lay the foundation for the research and development of new drugs and vaccines.

Objective:To identify the factors influencing acute kidney injury (AKI) following abdominal surgery in elderly patients and develop a predictive model based on the LASSO regression.Methods:The medical records of American Society of Anesthesiologists (ASA) Physical Status classificationⅠ-Ⅳ patients, aged ≥60 yr, with operation time ≥ 2 h, undergoing elective abdominal surgery under anesthesia in the General Hospital of Ningxia Medical University from May 2021 to May 2023, were retrospectively collected. AKI was diagnosed based on the Kidney Disease: Improving Global Outcomes organization guidelines. The patients were divided into 2 groups based on whether AKI occurred within 7 days after surgery: AKI group and non-AKI group. The least absolute shrinkage and selection operator algorithm was performed to reduce the dimension of unbalanced factors between AKI group and non-AKI group and the known risk factors for AKI. A nomogram prediction model was developed by integrating the optimized features derived from the LASSO regression model into multivariate logistic regression analysis. Internal validation was performed using the Bootstrap method, and the predictive ability and accuracy of the prediction model were assessed through the calibration curve, area under the receiver operating characteristic curve, Brier index and decision curve analysis.Results:Five hundred and ninety patients were finally included in this study, with 62 cases (10.5%) suffered postoperative AKI. The results of multivariate logistic regression analysis showed that increased age ( OR=1.06, 95% confidence interval [ CI] 1.01-1.11, P=0.048), higher ASA classification ( OR=2.32, 95% CI 1.21-4.45, P=0.011), preoperative coronary heart disease ( OR=1.89, 95% CI 1.01-3.61, P=0.049), and longer surgical duration ( OR=1.01, 95% CI 1.01-1.02, P=0.004) were risk factors for AKI after abdominal surgery, and the intraoperative use of dexmedetomidine ( OR=0.22, 95% CI 0.08-0.59, P=0.003) and increased postoperative albumin concentrations ( OR=0.91, 95% CI 0.85-0.98, P=0.017) were protective factors for postoperative AKI in elderly patients ( P<0.05). A risk prediction model was constructed based on the 9 identified factors of age, ASA classification, Charlson Comorbidity Index, preoperative coronary heart disease, preoperative hemoglobin concentration, preoperative estimated glomerular filtration rate, surgical duration, intraoperative use of dexmedetomidine and postoperative albumin concentration. A nomogram was plotted to visualize the model and verify it, showing that the Brier score of the model was 0.079, with a discrimination of 0.844, sensitivity of 84.4%, and specificity of 70.2%. Two hundred bootstrap resamples were used for internal validation, yielding a receiver operating characteristic curve of 0.821 with a 95% confidence interval of 0.79 to 0.90. The clinical decision curve indicated significant net benefits when the threshold probability of the model was between 0.03 and 0.45. Conclusions:Increased age, higher ASA classification, preoperative coronary heart disease, and longer surgical duration are risk factors, and the intraoperative use of dexmedetomidine and increased postoperative albumin concentrations are protective factors for postoperative AKI in elderly patients. The AKI prediction model following abdominal surgery developed based on age, ASA classification, Charlson Comorbidity Index, preoperative coronary heart disease, preoperative hemoglobin concentration, preoperative estimated glomerular filtration rate, surgical duration, intraoperative use of dexmedetomidine and postoperative albumin concentration has good predictive value in elderly patients.

The density and composition of lymphocytes infiltrating colon tumors serve as predictive factors for the clinical outcome of colon cancer.Our previous studies highlighted the potent anti-cancer properties of the principal compounds found in Garcinia yunnanensis(YTE-17),attributing these effects to the regu-lation of multiple signaling pathways.However,knowledge regarding the mechanism and effect of YTE-17 in the prevention of colorectal cancer is limited.In this study,we conducted isobaric tags for relative and absolute quantification(iTRAQ)analysis on intestinal epithelial cells(IECs)exposed YTE-17,both in vitro and in vivo,revealing a significant inhibition of the Wnt family member 5a(Wnt5a)/c-Jun N-terminal kinase(JNK)signaling pathway.Subsequently,we elucidated the influence and mechanism of YTE-17 on the tumor microenvironment(TME),specifically focusing on macrophage-mediated T helper 17(Th17)cell induction in a colitis-associated cancer(CAC)model with Wnt5a deletion.Additionally,we performed the single-cell RNA sequencing(scRNA-seq)on the colonic tissue from the Wnt5a-deleted CAC model to characterize the composition,lineage,and functional status of immune mesenchymal cells during different stages of colorectal cancer(CRC)progression.Remarkably,our findings demon-strate a significant reduction in M2 macrophage polarization and Th17 cell phenotype upon treatment with YTE-17,leading to the restoration of regulatory T(Treg)/Th17 cell balance in azoxymethane(AOM)/dextran sodium sulfate(DSS)model.Furthermore,we also confirmed that YTE-17 effectively inhibited the glycolysis of Th17 cells in both direct and indirect co-culture systems with M2 macrophages.Notably,our study shed light on potential mechanisms linking the non-canonical Wnt5a/JNK signaling pathway and well-established canonical β-catenin oncogenic pathway in vivo.Specifically,we proposed that Wnt5a/JNK signaling activity in IECs promotes the development of cancer stem cells with β-catenin activity within the TME,involving macrophages and T cells.In summary,our study undergoes the po-tential of YTE-17 as a preventive strategy against CRC development by addressing the imbalance with the immune microenvironment,thereby mitigating the risk of malignancies.

AIM:To explore the efficacy of lenvatinib(Len)in enhancing the therapeutic effects of immune checkpoint inhibitor for hepatocellular carcinoma(HCC)and to delve into its immunomodulatory mechanisms within the tumor microenvironment.METHODS:The effects of various concentrations of Len on the migration of human umbilical vein endothelial cells(HUVECs)and the secretion of CXC chemokine ligand 10(CXCL10)were investigated,and the mechanism by which Len modulates CXCL10 secretion was validated.An orthotopic HCC model was established,and the mice bearing tumors were randomly allocated into 4 groups:PBS group,BMS-202(PD-1/PD-L1 inhibitor)group,Len group,and Len/BMS-202 group.The progression of the orthotopic liver tumors was monitored with small animal in vivo im-aging techniques.On the 13th day after the treatment,mice were sacrificed and tumor tissues were harvested for analysis.Immunofluorescence was employed to identify apoptosis,vascular architecture,and hypoxic status within the tumor tis-sue.The expression levels of proliferation marker Ki67,transforming growth factor-β(TGF-β),and the infiltration de-grees of CD4+T cells and CD8+T cells in the tumor tissue were monitored with immunohistochemistry.The secretion of im-mune factors interferon-γ(IFN-γ),CXCL10 and TGF-α in the mouse serum was quantified with ELISA.Above all data were followed by statistical analysis.RESULTS:(1)Len could facilitate endothelial cell migration within a specific range and potentiated the response of tumor cells to IFN-γ by blocking fibroblast growth factor receptor(FGFR),thereby increasing the secretion of CXCL10 from the tumor cells.(2)Compared with PBS group,tumor growth was slower in all treatment groups,with Len/BMS-202 group showing the most significant inhibition of tumor growth in tumor-bearing mice(P<0.05).(3)Compared with PBS group and monotherapy groups,Len/BMS-202 significantly promoted tumor tissue apoptosis and inhibited tumor cell proliferation(P<0.05).(4)Compared with PBS group and BMS-202 group,both Len group and Len/BMS-202 group manifested a substantial enhancement in pericytes coverage rate(P<0.01),concomitantly showing a marked improvement in hypoxic conditions(P<0.01).(5)Compared with PBS group and monotherapy groups,Len/BMS-202 group showed a significant increase in the infiltration of CD4+T cells and CD8+T cells within the tumor(P<0.01),along with a marked decrease in the expression of TGF-β(P<0.01).(6)Compared with PBS group,all treatment groups collectively induced varying degrees of secretion of IFN-γ,CXCL10 and TGF-α in mouse serum(P<0.05),with Len/BMS-202 group demonstrating the most pronounced effects(P<0.01).CONCLUSION:Lenvatinib may augment the therapeutic efficacy of BMS-202 in HCC by facilitating tumor vascular normalization,alleviating hypoxic conditions,and enhancing the secretion of CXCL10,thereby synergistically activating the tumor immune microenvironment.

ObjectiveTo evaluate the effect of transcranial direct current stimulation (tDCS) on the cognitive function and quality of life in patients with Parkinson's disease. MethodsRandomized controlled trials (RCTs) on tDCS for Parkinson's disease were searched in PubMed, Web of Science, Embase, Cochrane Library, CNKI, CBM, VIP and Wanfang Data from the inception to September, 2023. Control group was administered standard Parkinson's medications or placebo, physical therapy, and cognitive rehabilitation, while treatment group received tDCS additionally. The quality of the researches was evaluated using the Cochrane Risk of Bias Tool. Data synthesis and analysis were performed using RevMan 5.4 and Stata 17.0, with heterogeneity and sensitivity analyses. ResultsEight articles were included. tDCS significantly improved the scores of Montreal Cognitive Assessment (MD = 2.00, 95%CI 1.13 to 2.87, P < 0.001). However, there was no significant difference in the scores of Parkinson's Disease Questionnaire (MD = 0.73, 95%CI -5.78 to 7.23, P = 0.830), Beck Depression Inventory-Ⅱ(MD = -0.77, 95%CI -7.14 to 5.60, P = 0.810), and Unified Parkinson Disease Rating Scale-Ⅲ (MD = 1.60, 95%CI -0.77 to 3.97, P = 0.190). ConclusiontDCS may improve cognitive function of patients with Parkinson's disease.

ObjectiveTo observe the clinical efficacy of modified Zuojinwan granules in treating reflux esophagitis （RE） and functional dyspepsia （FD） with the same syndrome with disharmony between liver and stomach）. MethodA randomized double-blind placebo-controlled clinical trial was conducted to enroll 144 patients with disharmony between liver and stomach， including 72 patients with RE and 72 patients with FD. These patients were then randomly divided into observation and control groups， with 36 patients in each group. The observation group was given modified Zuojinwan granules orally， and the control group was given placebo granules orally. They both were treated with two packs each time， twice a day， for four weeks. The traditional Chinese medicine （TCM） syndrome scores， cerebrointestinal peptides ［calcitonin gene-associated titanium （CGRP）， vasoactive intestinal peptide （VIP）， 5-hydroxytryptamine （5-HT）， and substance P （SP）］， inflammatory factors ［tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6）］， common gastrointestinal related hormones ［gastrin （GAS） and motilin （MTL）］， and other indicators in the two groups were compared before and after treatment， and the curative effect of TCM syndromes and the occurrence of adverse reactions were determined. At the same time， the changes in the above indicators and the curative effect of TCM syndromes in the two groups of patients with the same disease were analyzed. ResultAfter treatment， CGRP， VIP， 5-HT， SP， TNF-α， IL-6， GAS， MTL， and TCM syndrome scores in the observation group and control group were significantly improved （P<0.05）. After treatment， the improvement of CGRP， VIP， 5-HT， SP， TNF-α， IL-6， GAS， MTL， and TCM syndrome scores in the observation group was better than that in the control group （P<0.05）. After treatment， CGRP， VIP， 5-HT， SP， TNF-α， IL-6， GAS， MTL， and TCM syndrome scores in both groups of RE patients and FD patients were significantly improved （P<0.05）. After treatment， the improvement of CGRP， VIP， 5-HT， SP， TNF-α， IL-6， GAS， MTL， and TCM syndrome scores in RE patients and FD patients in the observation group were better than that in the control group （P<0.05）. In the observation group and the control group， the incidence of nausea， vomiting， fatigue， dry mouth， and other adverse reactions was lower， and there was no statistical significance. ConclusionModified Zuojinwan granules can effectively improve the TCM syndromes of disharmony between liver and stomach of RE and FD， brain and intestinal peptide， gastrointestinal hormone， and inflammatory factors and provide evidence for the clinical application of TCM theory of "treating different diseases with the same method".

Objective To investigate the predictive value of urinary exosomal microRNA(miR)-29 c in the clinical outcome of organ-and non-organ-confined bladder urothelial carcinoma(BUC).Methods From January 2017 to March 2022,152 patients with BUC were recruited from the Department of Urology in our hospital as a validation set.In addition,126 non-cancer controls were selected from the physical examination center of our hospital.The expression level of urinary exosomal miR-29c was detected by real-time quantitative PCR.Results In the validation set,urinary exosomal miR-29c level in BUC patients was significantly lower than that in non-cancer control group(P＜0.05),while urinary exosomal miR-17-5p level and miR-590-5p level were not significantly different(P＞0.05).The area under ROC curve of urinary exosomal miR-29c for the diagnosis of BUC was 0.969(95％CI:0.953～0.986),and the corresponding sensitivity and specificity were 92.1％and 90.2％,respectively.In subtype analysis,urinary exosomal miR-29c levels were further reduced in patients with non-organ-confined BUC compared with patients with organ-confined BUC(P=0.009).Overall survival(OS),disease-free survival(DFS)and disease-specific survival(DSS)were longer in the urinary exosomal miR-29c high expression group(P＜0.05).Conclusion Low levels of urinary exosomal miR-29c are an adverse prognostic factor for survival in patients with BUC,and are promising as a predictor of adverse clinical outcomes of organ-and non-organ-confined BUC.