Probiotics are natural systems bridging synthetic biology, physical biotechnology, and immunology, initiating innate and adaptive anti-tumor immune activity. We previously constructed an all-in-one engineered food-grade probiotic Lactococcus lactis (FOLactis) which could boost the crosstalk among different immune cells such as dendritic cells (DCs), natural killer cells, and T cells. Herein, considering the limited clinical efficacy of naked personalized neoantigen peptide vaccines, we decorate FOLactis with tumor antigens by employing a Plug-and-Display system comprising membrane-inserted peptides. Intranodal injection of FOLactis coated with neoantigen peptides (Ag-FOLactis) induces robust DCs presentation and neoantigen-specific cellular immunity. Notably, Ag-FOLactis not only triggers a 45-fold rise in the quantity of locally reactive neoantigen-specific T cells but also induces epitope spreading in both subcutaneous and metastatic tumor-bearing models, leading to potent inhibition of tumor growth. These findings imply that Ag-FOLactis represents a powerful platform to rapidly and easily display antigens, facilitating the development of a bio-activated platform for personalized therapy.

Objective:To investigate the real experience of early postoperative kinesiophobia in school-aged children after limb frac-ture surgery.Methods:A descriptive qualitative research method was used to conduct semi-structured interviews with sixteen children with limb fractures and their families in the ward of pediatric orthopedics in a grade A tertiary hospital in Chongqing,China,and a con-tent analysis was used to summarize and extract key themes from the interview data.Results:Three main themes and ten subthemes were extracted.The theme of pain cognition and catastrophic thinking included the subthemes of children's pain perception and activ-ity restriction,parents'pain perception and catastrophic reactions,and the interactive influence of pain cognition among different indi-viduals;the theme of medical education and risk perception included the subthemes of fear and concerns about refracture,the relation-ship between personality traits,help-seeking behavior,and internal-ized anxiety,and the impact of medical education on risk percep-tion;the theme of psychosocial stress and self-motivation included the subthemes of family members'attitudes toward academic inter-ruption,children's social disruption and compensatory media use,the mutual influence of compensatory indulgence and reinforced sick role behavior,and positive reinforcement enhancing children's self-driven recovery.Conclusion:Healthcare providers should closely monitor the recovery of limb motor function in the early stage af-ter surgery in children with fractures and provide personalized medical services and rehabilitation guidance to children and their fami-lies based on the pain perception,personality traits,and rehabilitation needs of children.

Objective:This study aimed to retrospectively analyze the incidence and influencing factors of tricuspid regurgitation (TR) in the short term after pacemaker lead implantation at the Second Affiliated Hospital of Zhejiang University School of Medicine, so as to provide evidence for understanding pacemaker lead-related TR.Methods:Consecutive patients who underwent single- or dual-chamber permanent pacemaker implantation between June 2019 and December 2023 in the Department of Cardiology were enrolled. General clinical data and relevant parameters were collected. Changes in TR severity before and shortly after the procedure were assessed using echocardiography. TR progression was defined as an increase by one grade or more, and TR improvement as a decrease by one grade or more. Logistic regression analysis was employed to identify factors associated with TR progression.Results:A total of 219 patients were included (128 males, 91 females), with a mean age of 69.7 ± 11.2 years. The median follow-up time was 99 (26, 199) days. TR remained unchanged in 114 patients (52.1%), improved in 46 (21.0%)—including 36 (16.4%) with one-grade reduction, 9 (4.1%) with two-grade reduction, and 1 (0.5%) with three-grade reduction—and progressed in 59 patients (26.9%). Among those with progression, 51 (23.3%) had mild-to-moderate TR worsening by one grade, and 8 (3.7%) had moderate or worse TR worsening by at least two grades. Notably, one case involved lead perforation of the leaflet and two cases had lead impingement. Compared with the non-progression group ( n = 114), pacemaker indication (AV block vs. sick sinus syndrome), baseline left atrial diameter, pulmonary artery systolic pressure (PASP), and the severity of mitral regurgitation (MR) and TR were significantly associated with TR progression or improvement (all P < 0.05). Ordinal logistic regression analysis identified preoperative TR severity [ OR=10.57 (3.77–29.68), P < 0.001] and pacemaker indication [ OR=0.452 (0.222–0.918), P = 0.028] as independent predictors of postoperative TR progression. Patients with AV block were more likely to receive left bundle branch pacing ( P < 0.001), which may contribute to their lower risk of TR. Conclusions:Short-term progression of TR after pacemaker implantation is relatively common, although severe TR remains rare. Preoperative TR severity and pacemaker indication are independent predictors of short-term TR progression. The use of physiological pacing modalities may help reduce the incidence of TR following pacemaker lead implantation.

Objective To analyze the clinical efficacy of transcatheter tricuspid valve replacement (TTVR) in cardiac implantable electronic lead-related tricuspid regurgitation (TR). Methods The patients with severe TR who underwent LuX-Valve TTVR in 9 Chinese medical centers from June 2020 to August 2021 were retrospectively enrolled. They were divided into a cardiac implantable electronic device (CIED) group and a non-CIED group based on whether they had pre-existing CIED implantation. Success of the procedure was defined as safe implantation of the LuX-Valve and complete withdrawal of the delivery system. Prognostic improvement was defined as a decrease of TR grade to≤2+ and an improvement of cardiac function by≥2 grades. Surgical success and postoperative prognosis were compared between the two groups. Results A total of 190 patients were collected, including 50 males and 140 females with a mean age of 66.2±7.8 years. There were 29 patients in the CIED group, and 161 patients in the non-CIED group. In the CIED group, 28 patients were implanted with a permanent pacemaker and 1 patient with a cardioverter-defibrillator. Preoperative New York Heart Association (NYHA) cardiac function class, TR degree, left ventricular ejection fraction, tricuspid annular plane systolic excusion, and cardiac risk scores were comparable between the two groups (P>0.05). Postoperative TR was reduced to≤2+ in all patients, and there was no statistical difference in the incidence of perivalvular leakage between the two groups (P=0.270). Postoperative CT of CIED patients showed the valve was in place, and the lead was not extruded, twisted, or deflected. The in-hospital mortality of the two groups were 10.3% and 1.9%, respectively, and the difference was statistically significant (P=0.047). In addition, there was no statistical difference between the two groups in terms of postoperative improvement of cardiac function and mortality in the 1- and 2-year follow-up. Conclusion TTVR is feasible, safe, and effective in patients with CIED implantation, and the pre-existing lead has no significant effect on the clinical efficacy.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

OBJECTIVE To correctly identify and deal with the adverse drug reaction as pancytopenia caused by isavuconazonium and to provide reference for the safe use of isavuconazonium. METHODS Clinical pharmacists analyzed a case of severe infection and renal insufficiency who experienced pancytopenia after using isavuconazonium. Clinical pharmacists screened the drugs used during hospitalization and evaluated the relationship between this adverse drug reaction and isavuconazonium， as well as the possible mechanisms， based on the half-life of the drugs and relevant literature. RESULTS & CONCLUSIONS The relationship between pancytopenia and isavuconazonium was assessed as “possibly related”. When using isavuconazonium， attention should be paid to avoiding the combination of drugs with the same mechanism or potential interaction. For patients who have a course of treatment for more than 2 weeks， have hematological abnormalities or complicated with liver and renal insufficiency， or should use it combined with other drug with same mechanism， it may be considered to increase the frequency of blood routine monitoring.

Objective To retrospectively analyze the efficacy and safety of low-dose antithymocyte globulin(ATG)combined with low-dose post transplantation cyclophosphamide(PTCY)in prevention of graft versus host disease(GVHD)after haploidentical transplantation.Methods Clinical data of 90 patients receiving haplotype matched transplantation in No.920 Hospital of PLA Joint Logistic Support Force from January 2022 to February 2023 were collected,and they were divided into study group(n=47)and control group(n=43)according to different GVHD prevention programs.The patients of the study group were given low-dose ATG combined with low-dose PTCY,and those of the control group received standard dose of PTCY.The implantation status,occurrence of GVHD,survival status and other indicators were analyzed between the 2 groups.Results ① Both groups of patients were successfully implanted,the median duration for neutrophil implantation(11 vs 17 d,P＜0.05)and platelet implantation(12 vs 20 d,P＜0.05)was significantly shorter in the study group than the control group.The incidence of grade Ⅱ～Ⅳ aGVHD(12.8％vs 34.9％,P＜0.05)and grade Ⅲ～Ⅳ aGVHD(6.4％ vs 20.9％,P＜0.05)was significantly lower in the study group than the control group,so was the non-recurrent mortality rate(6.4％vs 20.9％,P＜0.05)and the incidence of hemorrhagic cystitis(12.8％ vs 34.9％,P＜0.05).② By the end of the study,there were no significant differences in the incidence of mild and moderate and severe cGVHD,recurrence rate,reactivation rates of EBV and CMV,overall survival rate or progression-free survival rate between the 2 groups.Conclusion For haploidentical transplantation,low-dose ATG combined with low-dose PTCY has the advantages of lower incidence of GVHD,non-recurrent mortality,incidence of hemorrhagic cystitis and faster implantation.

Objective To preliminarily explore the efficacy of chimeric antigen receptor T cells(CAR-T)targeting CD 123 in the treatment of acute myeloid leukemia(AML)and the role of dasatinib in the treatment of CD123 targeting CAR-T induced side effects.Methods Clinical data of 1 patient with relapsed AML admitted to No.920 Hospital of PLA Joint Logistic Support Force in September,2019 were collected.The patient relapsed after previous multi-line chemotherapy and was treated with CD123 targeting CAR-T therapy.The routine blood changes of the patient after treatment were observed.Dasatinib was used when agranulocytosis occurred,40 mg orally 3 times per day,and was stopped when agranulocytosis was relieved.Changes in blood cells,CAR-T amplification,and disease control were observed.The patient was followed up for over 1 year.Results Flow cytometry for bone marrow showed that minimal residual disease negative result was observed in 30 d after infusion.The patient remained disease-free for over 1 year.After CD 123 CAR-T cells infusion,significant expansion of CAR-T cells was observed,accompanied by granulocyte deficiency and cytokine release syndrome(CRS).After using dasatinib,inhibition of CAR-T cell expansion was observed,accompanied by blood cell recovery,and CRS symptoms were alleviated.After stop of dasatinib,CAR-T cells expanded again and blood cells decreased again.Conclusion CAR-T cells targeting CD 123 have certain efficacy in the treatment for relapsed AML.Dashatinib has a blocking effect on the amplification and function of CAR-T,which can alleviate bone marrow suppression caused by CD 123 targeting CAR-T and avoid severe CRS.

Objective To compare the discrepancies among results of three commonly used laboratory direct test methods for maximal oxygen uptake(VO2max),explore their linear regression relationships,mutual predictability and comparability.Methods Using a quasi-experimental design of cluster sampling and within-group interaction design,20 male cross-country skiers were tested for VO2max using the Bruce protocol(Method 1),90-second incremental load exercise on power bicycle(Method 2),and 1-minute incremental load exercise on treadmill(Method 3),with an interval of one week.The indepen-dent and dependent variable were the three VO2max test methods and the VO2max,respectively.Results Significant differences were found in the average VO2max of the three test results,with the value mea-sured by Method 1 ranking the first,followed by that assessed by Method 3 and Method 2(P<0.05).Moreover,the frequency of individual differences in the results of the three methods showed that the VO2max of Method 1 was about 6 and 3 ml/min·kg higher than that measured by Method 2 and 3.However,at the same treadmill speed,the average blood lactate evaluated using Method 3 was higher than Method 1,and the speed reached aerobic and anaerobic thresholds about one speed unit(1 km/h)lower than Method 1.Meanwhile,linear regression analyses of the test results between Method 1 and 2,as well as Method 1 and 3 showed that both the regression models and coefficients were statis-tically significant(P<0.001),with the R-squared values of 9.25 and 9.05,respectively.Conclusion The Bruce protocol performs best in assessing the maximum value of the athlete's VO2max phase,whose results have linear regression relationships with the other two methods,and can be used for pre-dicting their results.Moreover,athletes of different events and levels can choose different VO2max test methods accordingly.Lastly,the speed and heart rate ranges corresponding to the aerobic and anaero-bic thresholds can serve as an effective and convenient method to control the training intensity.

Objective:To investigate and verify a novel acute graft versus host disease (aGVHD) prevention protocol in the context of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) .Methods:Patients who underwent haplo-HSCT in our center between January 2022 and December 2022 were included. All patients received reduced doses of cyclophosphamide, Rabbit anti-human tymoglobulin, ruxolitinib, methotrexate, cyclosporine, and MMF to prevent aGVHD. The transplantation outcomes, complications, and survival rate of all patients were investigated.Results:A total of 52 patients with haplo-HSCT were enrolled, 29 (55.8%) male and 23 (44.2%) female, with a median age of 28 (5-59) years. There were 25 cases of acute myeloid leukemia, 17 cases of acute lymphocyte leukemia, 6 cases of myelodysplastic syndrome, 2 cases of chronic myeloid leukemia and 2 cases of myeloproliferative neoplasms. 98.1% of patients had successful engraftment. The incidence of Ⅱ-Ⅳ aGVHD and Ⅲ-Ⅳ aGVHD was 19.2% (95% CI 8.2% -30.3% ) and 7.7% (95% CI 0.2% -15.2% ), respectively. No patients experienced severe gastrointestinal mucositis. The Epstein-Barr virus and CMV reactivation rates were 40.4% and 21.3%, respectively. 9.6% of patients relapsed during followup, with 1-year overall survival, progression-free survival, and non-relapse mortality rates of 86.5% (95% CI 76.9% -96.1% ), 78.8% (95% CI 67.4% -90.3% ) and 11.5% (95% CI 2.6% –20.5% ), respectively. Conclusion:Ruxolitinib combined with a low dose of PTCY is a safe and effective first-line aGVHD prevention strategy.