Fanconi anemia (FA) is an inheritable disorder that presents with bone marrow failure, developmental anomalies, and an increased susceptibility to cancer. The etiology of this condition stems from a genetic mutation that disrupts the proper repair of interstrand DNA cross-links (ICLs). The resultant dysregulation of the DNA damage response mechanism can induce genomic instability, thereby elevating the mutation rates and the likelihood of developing cancer. The FA pathway assumes a pivotal role in safeguarding genome stability through its involvement in the repair of DNA cross-links and the maintenance of overall genomic integrity. A mutation in the germ line of any of the genes responsible for encoding the FA protein results in the development of FA. The prevalence of aberrant FA gene expression in somatic cancer, coupled with the identification of a connection between FA pathway activation and resistance to chemotherapy, has solidified the correlation between the FA pathway and cancer. Consequently, targeted therapies that exploit FA pathway gene abnormalities are being progressively developed and implemented. This review critically examines the involvement of the FA protein in the repair of ICLs, the regulation of the FA signaling network, and its implications in cancer pathogenesis and prognosis. Additionally, it explores the potential utility of small-molecule inhibitors that target the FA pathway.

Immunology courses are offered in the majors of biology,medicine,animal husbandry and food in Chinese colleges and universities.Due to the characteristics of multi-dimensional composition of immunology knowledge,most students are not easy to understand the logical relationship between key points and knowledge points in learning,and will encounter problems such as unable to keep up with the teaching pace,lack of confidence in learning,feeling complex association between the knowledge points of chap-ters,and not fully understanding the immunology knowledge points.This paper summarizes the teaching methods of heuristic,main line and case in Immunology teaching,so as to solve the difficulties in learning,clarify learning ideas,improve learning confidence and learning effectiveness.

AIM:To investigate the therapeutic effect of raddeanin A(RA)on prostate cancer xenograft mouse model,and to explore its potential mechanisms.METHODS:(1)Western blot analysis was used to investigate the effects of different concentrations(0,0.5,1,2 and 4 μmol/L)of RA on the expression of programmed cell death li-gand 1(PD-L1)protein in prostate cancer cell lines PC-3,DU145 and RM-1.(2)Thirty C57BL/6J mice were randomly divided into blank group,low-dose RA group,and high-dose RA group,with 10 mice in each group.The mice in low-and high-dose RA groups were intraperitoneally injected with 2 and 4 mg/kg RA continuously for 24 d,respectively.Mouse body weight was recorded,and tumor volume and weight were measured.Immunohistochemistry experiments were con-ducted to detect the expression of Ki67 and PD-L1 proteins in mouse tumor tissues.Flow cytometry was used to determine the percentages of CD8+T cells,CD4+T cells and regulatory T cells(Treg),as well as the levels of interferon-γ(IFN-γ)and granzyme B(GzmB)in tumor tissues.RESULTS:Treatment with RA significantly reduced the expression of PD-L1 in PC-3,DU145 and RM-1 cells(P<0.05 or P<0.01).In vivo experiments showed that RA treatment led to significant decreases in tumor volume and weight(P<0.05 or P<0.01).Additionally,the expression levels of Ki67 and PD-L1 in tu-mor tissues were significantly reduced(P<0.05 or P<0.01).Furthermore,RA treatment significantly increased the per-centages of CD8+T cells and CD4+T cells within mouse tumors,elevated the levels of IFN-γ and GzmB,and reduced the number of activated Treg(P<0.05 or P<0.01).CONCLUSION:The RA exhibits potent inhibitory effects on tumor growth in a prostate cancer xenograft mouse model.Its mechanism may be associated with the inhibition of PD-L1 expres-sion,increased infiltration of tumor-infiltrating T cells,and suppression of Treg.

【Objective】 To investigate the situation of carbapenem-resistant Enterobacteriaceae(CRE) colonization in patients undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT). 【Methods】 A total of 241 consecutive patients who underwent haplo-HSCT in the First Affiliated Hospital of Soochow University from June 1, 2021 to June 1, 2022 were enrolled. Anal swab screening was performed within 48 hours of admission and blood cultures were taken when the patient developed fever. Univariate and multivariate analysis were used to analyze the colonization rate, distribution, risk factors and the correlation between CRE colonization and post-transplant bloodstream infection(BSI). 【Results】 Among 241 patients with haplo-HSCT, there were 90 cases in CRE colonization positive group, with a colonization rate of 37.3% (90/241). Multivariate logistic regression analysis showed that sex (OR 2.42, 95% CI 1.38-4.22, P<0.05) and history of infection within 30 days before transplantation (OR 3.37, 95% CI 1.59-7.17, P<0.05) may be independent risk factors for CRE intestinal colonization. Of the 95 CRE strains, the top five species were carbapenem-resistant Klebsiella pneumoniae (38/95, 40.0%), carbapenem-resistant Escherichia coli (29/95, 30.5%), carbapenem-resistant Enterobacter cloacae (13/95, 13.6%), carbapenem-resistant Klebsiella acidophilus (6/95, 6.3%) and carbapenem-resistant Proteus mirabilis (3/95, 3.1%). The incidence of post-transplant BSI was 12.0% (29/241) in the CRE-colonized group and 3.3% (8/241) in the non-colonized group. In the colonization group, 100% of the pathogens of BSI were identical with those of CRE colonization. 【Conclusion】 Bacterial culture of anal swab during haplo-HSCT is helpful for detection of CRE colonization in intestinal tract, which provides some clinical basis for active monitoring of key flora, prevention and control of infection.

Enzalutamide (ENZ) is a second-generation androgen receptor (AR) antagonist used for the treatment of castration-resistant prostate cancer (CRPC) and reportedly prolongs survival time within a year of starting therapy. However, CRPC patients can develop ENZ resistance (ENZR), mainly driven by abnormal reactivation of AR signaling, involving increased expression of the full-length AR (ARfl) or dominantly active androgen receptor splice variant 7 (ARv7) and ARfl/ARv7 heterodimers. There is currently no efficient treatment for ENZR in CRPC. Herein, a small molecule LLU-206 was rationally designed based on the ENZ structure and exhibited potent inhibition of both ARfl and constitutively active ARv7 to inhibit PCa proliferation and suppress ENZR in CRPC. Mechanically, LLU-206 promoted ARfl/ARv7 protein degradation and decreased ARfl/ARv7 heterodimers through mouse double minute 2-mediated ubiquitination. Finally, LLU-206 exhibited favorable pharmacokinetic properties with poor permeability across the blood-brain barrier, leading to a lower prevalence of adverse effects, including seizure and neurotoxicity, than ENZ-based therapies. In a nutshell, our findings demonstrated that LLU-206 could effectively inhibit ARfl/ARv7-driven CRPC by dual-targeting of ARfl/ARv7 heterodimers and protein degradation, providing new insights for the design of new-generation AR inhibitors to overcome ARfl/ARv7-driven CRPC.

Objective:To detect and analyze the infections of respiratory pathogens in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Methods:Through retrospective analysis, 335 AECOPD patients hospitalized from October 2016 to September 2018 in the First People′s Hospital of Pinghu were selected.The indirect immunofluorescence method was used to detect IgM antibody of eight kinds of respiratory pathogens, and the results were analyzed.Results:The positive rate of respiratory pathogens-IgM antibody in patients with AECOPD was 29.9%.There were 57 cases with one single pathogen infection, 36 cases with two pathogens mixed infection, 7 cases with three kinds of pathogens mixed infection.The influenza virus B [52.0%(78/150)] was the most common, followed by influenza virus A [27.3%(41/150)], the positive rates of pathogens were influenza virus B>influenza virus A>respiratory syncytial virus>parainfluenza virus>Legionella pneumophila>Mycoplasma pneumoniae>Chlamydia pneumoniae>adenovirus.There was no statistically significant difference in different age groups(χ 2=0.047, P=0.829). The positive rates of pathogens-IgM in spring[55.3%(63/114)] and winter[58.1%(54/93)] were higher than those in summer[26.2%(16/61)] and autumn[25.4%(17/67)], the differences were statistically significant(χ 2=30.398, P<0.01). Conclusion:AECOPD is closely related with respiratory pathogens, especially influenza virus.We should do preventive work well in epidemic season.

Objective: : To explore the effect of PD-1 gene knockout by CRISPR/Cas9 system on the proliferation and IFN-γ secretion in human T cells. Methods: : The sequence of sgRNA targeting PD-1 was designed. The PD-1-sgRNA and Cas9 mRNA were synthesized by T7 RNApolymerase in vitro, and then the mixture of PD-1-sgRNAand Cas9 mRNAwas delivered into activated T cells by nucleofection. The efficiency of gene knockout was confirmed by sequencing. The phenotypes of T lymphocytes and the expression of PD-1 after gene knockout were analyzed by Flow cytometry. The proliferation of T lymphocytes was calculated by trypan blue counting. The level of IFN-γ secreted by T lymphocytes was detected by ELISA. Results： ：PD-1-sgRNA and Cas9 mRNA were successfully synthesized in vitro and delivered into T cells by nucleofection. Sequencing technology confirmed that the PD-1 gene sequence was edited and the editing efficiency was 58.3%. The expression of PD-1 on T lymphocyte surface was down-regulated successfully by CRISPR/Cas9 system [(9.6±1.85)% vs (16.2±2.05)%, P<0.05]. The knockout of PD-1 gene did not affect the proliferation and phenotype of T lymphocytes(P<0.05); However, compared with the control group, the level of IFN-γ secreted by T lymphocytes in the PD-1sgRNA group was significantly increased (P<0.01). Conclusion: : CRISPR/Cas9 system can successfully ablate PD-1 gene in human T lymphocytes, which could block the negative regulation of PD-1／PD-L1 and further promote the IFN-γ secretion in T cells.

About 15% to 20% of patients with small cell lung cancer(SCLC)have brain metastases at the time of initial di-agnosis,and more than 80% of patients eventually develop brain metastases. Whole brain radiotherapy(WBRT) is the standard treat-ment for brain metastases in lung cancer. Whole brain prophylactic irradiation(PCI)is an effective treatment for preventing brain me-tastases in SCLC. With the improvement of treatment technology and the standard of treatment,the survival of SCLC patients is pro-longed. The use of spiral tomography(TOMO) technology for hippocampal-protected WBRT in PCI or brain metastasis can reduce neurocognitive impairment and improve the life quality of patient.

Objective To investigate the value of real-time virtual navigation system (RVS) combined with CEUS in guiding radiofrequency ablation (RFA) therapy of neonatal or recurrent lesions of hepatocellular carcinoma (HCC).Methods Totally 111 patients with neonatal or recurrent lesions of HCC after RFA therapy were enrolled.Seventy-eight patients with 86 lesions (77 neonatal lesions and 9 recurrent lesions) underwent RFA guided by RVS combined with CEUS (RVS combined with CEUS group),and 33 patients with 38 lesions (26 neonatal lesions and 12 recurrent lesions) underwent RFA guided by CEUS alone (control group).The precise localization,inactivation rate and local recurrence rate between the two groups were compared.Results Eighty-four lesions (84/86,97.67％) in RVS combined with CEUS group and 25 lesions (25/38,65.79％) in control group were clearly showed and localized (P＜0.001).One month after RFA therapy,the tumor inactivation rate in RVS combined with CEUS group and control group was 95.35 ％ (82/86) and 76.31％ (29/38),respectively (P=0.003).The local recurrence rate in RVS combined with CEUS group was 8.14％ (7/86),while was 36.84％ (14/38) in control group (x2 =15.434,P＜0.001).Conclusion RVS combined with CEUS guidance can improve the accurate position rate and early inactivation rate of RFA therapy for neonatal or recurrent lesions of HCC.

Objective To study the application of BNP,NT-proBNP and ST2 in diagnosis of heart failure (HF).Methods Ninety-seven HF patients admitted to our hospital served as a HF group and 61 HF-free patients served as a control group.The patients in HF group were further divided in to class Ⅱ group (n=32),class Ⅲ group (n=36) and class Ⅳ group (n=29) according to their cardiac function in NYHA classification.The serum ST2,BNP and NT-proBNP levels were measured and their value in diagnosis of HF was analyzed.Results The serum BNP,NT-proBNP and ST2 levels were significantly higher in HF group than in control group (396.0 ng/L vs 39.4 ng/L,P＜0.01;1825.0 ng/L vs 215.0 ng/L,P＜0.01;56.8 μg/L vs 25.4 μg/L,P＜0.01),which increased with the increasing cardiac function in NYHA classification (P＜0.01).The area under the ROC curve for BNP,NT-proBNP,ST2,combined NT-proBNP and ST2 was 0.874,0.891,0.842,0.905 respectively for the diagnosis of HF.Conclusion BNP,NT-proBNP and ST2,3 new biomarkers,can improve the diagnosis of HF.