Metastatic dissemination is the major cause of death from breast-cancer (BC). Fusobacterium nucleatum (F.n) is widely enriched in BC and has recently been identified as one of the high-risk factors for promoting BC metastasis. Here, with an experimental model, we demonstrated that intratumoral F.n induced BC aggressiveness by transcriptionally activating Epithelial-mesenchymal transition-associated genes. Therefore, the F.n may be a potential target to prevent metastasis. Given the fact that cancer-associated fibroblasts (CAFs) are abundant in BC and located near blood vessels, we report an optogenetic system that drives CAF to in situ produce human antibacterial peptide LL37, with the characteristics of biosafety and freely intercellular trafficking, for depleting intratumoral F.n, leading to a 72.1% reduction in lung metastatic nodules number without affecting the balance of the systemic flora. Notably, mild photothermal treatment was found that could normalize CAF, contributing to synergistically inhibiting BC metastasis. In addition, the system can also simultaneously encode a gene of TNF-related apoptosis-inducing ligand to suppress the primary tumor. Together, our study highlights the potential of local elimination of tumor pathogenic bacteria to prevent BC metastasis.

Objective:To explore the clinical characteristics, diagnosis, treatment, and follow-up of multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 Omicron variant infection.Methods:A retrospective analysis was conducted on clinical data of 11 children with MIS-C, who were admitted to the Department of Pediatrics of Peking University First Hospital from December 2022 to January 2023. Clinical characteristics, treatment, and follow-up of MIS-C were summarized in this study.Results:The 11 cases contained 7 boys and 4 girls, with an age of 4.4 (2.0, 5.5) years on admission. All the patients had fever, with a duration of 7(5, 9) days. Other clinical manifestations included rash in 7 cases, conjunctival hyperemia in 5 cases, red lips and raspberry tongue in 3 cases, lymphadenopathy in 3 cases, and swollen fingers and toes in 2 cases. There were 8 cases of digestive symptoms, 8 cases of respiratory symptoms, and 3 cases of nervous system symptoms. Eight patients had multi-system injuries, and one of them had shock presentation. All 11 patients were infected with SARS-CoV-2 Omicron BF.7 variant. The laboratory examination results showed that all cases had elevated inflammatory indicators, abnormal coagulation function and myocardial damage. Six patients had elevated white blood cell counts, 5 cases had liver function abnormalities, 3 cases had kidney function abnormalities, and 8 cases had coronary artery involvement. All 11 patients received anti-infection treatment, of which 3 cases received only 2 g/kg intravenous immunoglobulin (IVIG), while the remaining 8 cases received a combination of IVIG and 2 mg/(kg·d) methylprednisolone. Among the 8 cases with coronary artery disease, 6 cases received low molecular weight heparin anticoagulation therapy. All patients were followed up in 2 weeks after being discharged, and their inflammatory markers had returned to normal by that time. The 8 cases with coronary artery disease and 3 cases with pneumonia showed significant improvement or back to normal at the 4-week follow-up. All patients had no new complications or comorbidities during follow-up of more than 3 months.Conclusions:MIS-C may present with Kawasaki disease-like symptoms, with or without gastrointestinal, neurological, or respiratory symptoms. Elevated inflammatory markers, abnormal coagulation function, and cardiac injury contribute to the diagnosis of MIS-C. IVIG and methylprednisolone were the primary treatments for MIS-C, and a favorable short-term prognosis was observed during a follow-up period of more than 3 months.

Objective To explore the predictive effect of empowerment and theory of planned behavior(TPB)on the four core behaviors of type 2 diabetes mellitus(T2DM)self-management,and analyze the influence path of TPB model and behavioral intention on the four core behaviors.Methods A total of 500 T2DM patients who were hospitalized in the Endocrinology Department of three tertiary general hospitals in different provinces from December 2022 to May 2023 were selected for investigation.Hierarchical multiple regression analysis was used to explore the predictive effects of empowerment and TPB models on self-management behaviors.Bootstrap method was used to analyze the influence path of TPB model and behavior intention on self-management behaviors.Results Empowerment had a predictive effect on self-management behavior,which was improved after the addition of TPB,with medication R2=0.194,blood glucose monitoring R2=0.308,regular diet R2=0.337 and regular exercise R2=0.343,respectively.Mediation effect analyses revealed that attitude,subjective norm,and perceived behavioral control were observed to predict behavior intention across the four behaviors,and the three except through the behavior intention indirectly affect behavior,can also directly affect the behavior.Conclusions Empowerment can predict self-management behavior,and adding TPB to this can improve the prediction effect.Attitude,subjective norms and perceived control can indirectly or directly affect self-management behavior through behavioral intention.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective To analyze the causal relationship between serum sex steroid hormone levels and myopia with the Mendelian randomization(MR)methods.Methods Sex hormone genetic tools classified by sex were publicly availa-ble summarized statistical data from the Genome-wide association study(GWAS)of the UK Biobank Consortium on sex hormone-binding globulin(SHBG),total testosterone(TT),bioavailable testosterone(BT),and estradiol(E2).The GWAS summarized statistical data for myopia were obtained from publicly available data published by the FinnGen Consorti-um R10.All data were downloaded from April 18 to April 31,2024 from the corresponding databases and analyzed.All re-sults from the MR study were mainly analyzed by inverse-variance weighting(IVW)method.Results The study showed that a higher serum SHBG level in European increased the risk of myopia development in women(IVW,OR=1.152,95％CI:1.014-1.308,P=0.029);low serum TT level(IVW,OR=0.821,95％CI:0.697-0.967,P=0.018)and serum BT lev-el(IVW,OR=0.820,95％CI:0.691-0.972,P=0.022)increased the risk of myopia development in women.There was no causal relationship between serum SHBG,TT,and BT levels and myopia in men.There was no causal effect between E2 level and myopia in women and men.The stability of our findings was supported by sensitivity analysis.Conclusion In-creased serum SHBG level and decreased serum TT and BT levels are associated with an increased risk of myopia in women,whereas no such association is found in men.There is no causal relationship between E2 and myopia.

Pulmonary mucinous adenocarcinoma is a subtype of lung adenocarcinoma, among which invasive mucinous adenocarcinoma (IMA) is the most common subtype and is easily misdiagnosed as pneumonia. Its etiology and pathogenesis are unclear and may be related to gene mutations and other factors. Due to its relative rarity and few related studies, guidelines do not provide advices on its treatment. KRAS mutations are common in IMA patients, and Sotorasib may be effective against KRAS G12C mutated IMA. NRG1 fusion is considered to be an important driver of IMA, and afatinib may be effective in treating IMA with NRG1 fusion/rearrangement. PD-L1 expression is very low in IMA patients, while B7-H3 expression is high, so B7-H3 may be a potential immunotherapeutic target.

Hepatocellular carcinoma (HCC) is an aggressive human cancer with increasing incidence worldwide. Multiple efforts have been made to explore pharmaceutical therapies to treat HCC, such as targeted tyrosine kinase inhibitors, immune based therapies and combination of chemotherapy. However, limitations exist in current strategies including chemoresistance for instance. Tumor initiation and progression is driven by reprogramming of metabolism, in particular during HCC development. Recently, metabolic associated fatty liver disease (MAFLD), a reappraisal of new nomenclature for non-alcoholic fatty liver disease (NAFLD), indicates growing appreciation of metabolism in the pathogenesis of liver disease, including HCC, thereby suggesting new strategies by targeting abnormal metabolism for HCC treatment. In this review, we introduce directions by highlighting the metabolic targets in glucose, fatty acid, amino acid and glutamine metabolism, which are suitable for HCC pharmaceutical intervention. We also summarize and discuss current pharmaceutical agents and studies targeting deregulated metabolism during HCC treatment. Furthermore, opportunities and challenges in the discovery and development of HCC therapy targeting metabolism are discussed.

Objective:To explore the effects of Pender's health promotion model in nursing interventions for patients undergoing hematopoietic stem cell transplantation.Methods:Totally 92 patients who underwent hematopoietic stem cell transplantation at the Department of Hematology, Ningbo First Hospital from January 2018 to December 2020 were selected by convenient sampling, and divided into a control group and an intervention group according to the random number table, with 46 patients in each group. Patients in the control group received routine care, while patients in the intervention group were treated with Pender's health promotion model. The general information questionnaire, Self-Perceived Burden Scale (SPBS) , Adult Health Self-management Ability Assessment Scale, and Functional Assessment of Cancer Therapy-Bone Marrow Transplantation Scale (FACT-BMT) were used to investigate the patients and compare the differences in self-perceived burden, self-management ability, and quality of life of the two groups of patients before and after the intervention.Results:The total scores of physical burden, emotional burden, and self-perceived burden in the intervention group were lower than those in the control group; the scores of core management ability, disease-related knowledge, and self-monitoring in the intervention group were higher than those in the control group; the scores and total score of the quality of life in the intervention group were higher than those in the control group, and the differences were statistically significant ( P<0.05) . Conclusions:The application of Pender's health promotion model in patients receiving hematopoietic stem cell transplantation can reduce the patient's self-perceived burden and improve their self-management ability and quality of life, which is worth promoting in clinical practice.

Acute myeloid leukaemia (AML) is the most common form of acute leukaemia in adults, with increasing incidence with age and a generally poor prognosis. Almost 20% of AML patients express mutant isocitrate dehydrogenase 2 (mIDH2), which leads to the accumulation of the carcinogenic metabolite 2-hydroxyglutarate (2-HG), resulting in poor prognosis. Thus, global institutions have been working to develop mIDH2 inhibitors. SH1573 is a novel mIDH2 inhibitor that we independently designed and synthesised. We have conducted a comprehensive study on its pharmacodynamics, pharmacokinetics and safety. First, SH1573 exhibited a strong selective inhibition of mIDH2 R140Q protein, which could effectively reduce the production of 2-HG in cell lines, serum and tumors of an animal model. It could also promote the differentiation of mutant AML cell lines and granulocytes in PDX models. Then, it was confirmed that SH1573 possessed characteristics of high bioavailability, good metabolic stability and wide tissue distribution. Finally, toxicological data showed that SH1573 had no effects on the respiratory system, cardiovascular system and nervous system, and was genetically safe. This research successfully promoted the approval of SH1573 for clinical trials (CTR20200247). All experiments demonstrated that, as a potential drug against mIDH2 R140Q acute myeloid leukaemia, SH1573 was effective and safe.

Objective:To evaluate the discrimination, reliability and validity of the evaluation system of clinical nurse training based on post competency in hospitals of traditional Chinese and Western medicine.Methods:From August 2018 to January 2019, 271 clinical nurses from a three-A hospital were selected by convenient sampling method. The competency of clinical nurses was assessed on the spot by case tracking method. The discrimination, reliability and validity of the evaluation system were tested by item analysis, Cronbach's α coefficient and confirmatory factor analysis.Results:The evaluation system had good discrimination, reliability and validity. Among the four scales of the evaluation system, there were significant differences in the high score and the low score of all items ( P < 0.05). The Cronbach's α coefficient of each dimension of the four scales was 0.769-0.898. Four structural equation model diagrams were established, the AVE (average variance extracted) of each dimension was 0.51-0.74, factor load was 0.53-0.93, C.R. (composite reliability) was 0.79-0.91, and the discrimination validity was up to the standard. Conclusion:This system provides a reference for the establishment of scientific, objective, measurable and homogeneous clinical nurse training evaluation tools.