OBJECTIVE To systematically evaluate risk prediction models for chemotherapy-induced myelosuppression in pediatric patients with malignant tumors， evaluate their modeling strategies， key predictors， and predictive performance， and provide evidence-based references for clinical decision-making and research. METHODS A literature search was conducted across 11 databases， including CNKI， Wanfang Data， and PubMed， for relevant studies published before April 2025. Two reviewers independently performed literature screening and data extraction， and the risk of bias and applicability of the models were evaluated using the PROBAST tool. RESULTS Ultimately， seven studies were selected， of which four were English articles and three were Chinese articles， involving 12 risk prediction models. Although model discrimination was good （AUC 0.748-0.981）， only two models underwent external validation； furthermore， calibration was inadequately reported in three studies. PROBAST indicated that all models exhibited a high risk of bias， with major issues including a predominance of retrospective designs， inadequate sample representativeness， and lack of blinding. However， in terms of applicability， all models received favorable evaluations. In terms of modeling methods， most studies employed traditional logistic regression approaches to construct models， while only a minority introduced machine learning algorithms and conducted systematic comparisons among multiple algorithms. Models developed using machine learning methods significantly outperformed those constructed with traditional statistical methods. CONCLUSIONS The existing risk prediction models for myelosuppression after chemotherapy in children with malignant tumors demonstrate potential in clinical risk early warning. However， they generally suffer from design and methodological limitations， such as a predominance of retrospective single-center designs， few events per variable， opaque handling of missing data， and inconsistent reporting of model coefficients. Future studies should adopt prospective designs， incorporate machine learning with key clinical predictors， and follow TRIPOD reporting guidelines to enhance scientific rigor and clinical utility.

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.

Background::Intrauterine growth restriction (IUGR) is associated with adverse metabolic outcomes during adulthood. Histone modifications and changes in DNA methylation-affected genes are important for fetal development. This study aimed to investigate the epigenetic mechanisms in IUGR.Methods::IUGR models were established in Sprague–Dawley rats using a maternal nutritional restriction approach during pregnancy. The abundance of insulin-like growth factor 2 (IGF2), phosphoinositide 3-kinase (PI3K), AKT serine/threonine kinase 2 (AKT2), and peroxisome proliferators-activated receptor gamma coactivator 1 alpha (PGC-1α) was examined by real-time polymerase chain reaction (RT-PCR) and Western blotting analysis. Chromatin immunoprecipitation RT-PCR was employed to analyze histone modification in CCCTC-binding factor (CTCF) 1–4 binding sites of the Igf2/H19 imprinting control region (ICR). The methylation states of CTCF1–4 binding sites were studied by pyrosequencing. Results::The IUGR models were constructed successfully. Igf2 mRNA abundance in the placenta, fetal liver, and newborn liver was decreased in the IUGR group ( P <0.01). Meanwhile, as compared with the control group, the expression levels of AKT2, PI3K, and PGC-1α were lower in newborn and 8-week-old livers in the IUGR group ( P <0.05). In addition, knocking down Igf2 reduced the protein expression levels of AKT2-phosphorylation and PGC-1α ( P <0.05). In CTCF binding sites 1-4 of the Igf2/ H19 ICR, acetylated histones H3 (AcH3) enrichment was significantly lower in CTCF1-3 in newborn and 8-week-old IUGR rats. Histone H3 tri-methylated lysine 4 (H3K4me3) enrichment was significantly lower in the CTCF1–4 of newborn and 8-week-old IUGR groups ( P <0.01). H3K9me2 enrichment was significantly higher in the IUGR group ( P <0.01). The CpG dinucleotide methylation levels of CTCF1 and CTCF3, but not those of CTCF2 and CTCF4 binding sites in IUGR rat fetal, 4-week old, and 8-week-old livers decreased significantly ( P <0.05). Conclusion::The methylation status and histone modification in the Igf2/H19 ICR are related to growth and lipid metabolism via the PGC-1α/PI3K/AKT2 pathway in IUGR rats.

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.

The Wnt signaling pathway plays an important role in maintaining liver homeostasis and liver regeneration.In healthy livers,the Wnt signaling pathway is mostly inactive,but it is continuously overactivated during cell renewal or regeneration processes,as well as in certain pathological conditions,diseases,precancerous states,and cancers.Persistent liver cell injury often leads to chronic liver diseases such as liver fibrosis,liver cirrhosis,and liver cancer.This article summarizes the basic structural features of the Wnt signaling pathway and analyzes its important role in the pathological progression of various liver diseases,so as to provide new ideas for the prevention and treatment of liver diseases in clinical practice.

Lipid metabolism,as the basis of life maintenance,is a prerequisite for cell survival,and lipid homeostasis can rapidly respond to metabolic changes in a coordinated manner.In cancers,there is an increase in lipid metabolism in cancer cells to meet the requirements for plasma membrane synthesis and energy production.Abnormal lipid metabolism plays an important role in the progression of primary liver cancer.This article reviews the association between abnormal lipid metabolism and primary liver cancer,in order to find targets for the prevention and treatment of primary liver cancer.

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 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.