[摘 要] 目的：探讨X连锁锌指蛋白（ZFX）通过Nectin-4表达影响食管鳞状细胞癌（ESCC）进展的分子机制及其对PI3K/AKT信号通路的激活作用。方法：收集2022年8月至2023年7月在南充市中心医院手术切除的30对ESCC组织及癌旁组织标本。采用人食管上皮细胞HET-1A及ESCC细胞KYSE-30、KYSE-150、KYSE-410、KYSE-510和TE-1。基于2018年至2019年收集的6例ESCC配对标本转录组测序数据筛选Nectin-4，通过TIMER2.0数据库、RT-qPCR和WB法、免疫组织化学（IHC）检测ESCC组织及细胞中Nectin-4的表达水平。采用shRNA技术在KYSE-410和KYSE-510细胞中敲低Nectin-4，通过CCK-8、克隆形成、划痕愈合及Transwell实验检测敲低Nectin-4对细胞增殖、迁移和侵袭能力的影响，采用WB法检测敲低Nectin-4对细胞PI3K/AKT通路及EMT相关蛋白表达水平的影响。通过生物信息学预测并结合双萤光素酶报告基因实验，鉴定并验证ZFX作为Nectin-4的上游转录调控因子。结果：综合分析显示，ESCC组织及细胞系中Nectin-4表达显著高于癌旁组织及HET-1A细胞（均P < 0.01）。功能研究表明，敲低Nectin-4显著抑制KYSE-410和KYSE-510细胞的增殖活性、克隆形成能力，以及迁移和侵袭能力（均P < 0.01）。机制方面，敲低Nectin-4时细胞中E-cadherin表达上调、N-cadherin下调（均P < 0.01），并抑制PI3K/AKT通路相关蛋白的磷酸化水平（P < 0.01）。结论： ZFX通过上调Nectin-4表达激活PI3K/AKT信号通路促进ESCC进展，为ESCC的治疗提供了潜在的新靶点。

Objective:To observe the applying effect of teamwork cooperation model of encephalopathy in the clinical teaching of Neurology.Methods:Sixty undergraduate students who practiced in our hospital were randomly divided into the control group and the experimental group,with 30 students in each group.The control group was arranged for internship according to the traditional department-based model,while the experimental group was arranged according to the teamwork cooperation model of encephalopathy discipline group.The theoretical examination scores and clinical skills scores of the two groups were compared,and the Mini-Clinical Evaluation Exercise(Mini-CEX)scale was used for dual evaluation by teachers and students from seven aspects:inquiry skills,physical examination skills,humanistic care,clinical judgment,communication skills,organizational effectiveness,and overall clinical competence.Result:There were statistically significant differences between the experimental group and the control group in theoretical examination scores,clinical skills scores,and dual evaluation by teachers and students(P＜0.05).Conclusion:Compared with the traditional teaching model,the teamwork cooperation model of encephalopathy discipline group has achieved better results in the clinical teaching of Neurology.

MicroRNA(miRNA)serves as a novel regulatory factor in viral and bacterial co-infections,exhibiting dual regulatory roles during pathogen infections.On the one hand,it exerts protective effects by modulating viral replication cycles and host anti-infection immune responses.On the other hand,it can be exploited by pathogens to promote infection progression,including influencing viral replication,antiviral immune responses,and regulating bacterial adhesion and proliferation.Mixed viral and bacterial infections lead to high mortality rates.By binding to specific target gene mRNA,miRNA degrades or inhibits its translation,thereby regulating target gene expres-sion,which may ultimately serve as potential diagnostic and therapeutic targets.This paper reviews recent ad-vances in research on the role of miRNA in viral and bacterial infections,particularly its mechanisms in co-infec-tions,aiming to provide theoretical reference for further research on the infection mechanisms.

Objective:To explore the relationship between spindle and kinetochore-associated protein 3(SKA3), dual-specificity phosphatase 26(DUSP26), and prognosis in elderly patients with non-small cell lung cancer(NSCLC).Methods:A retrospective analysis was conducted on case samples from elderly patients with NSCLC at Xinxiang Central Hospital between January 2020 and May 2023.During surgery, specimens of cancerous and adjacent non-cancerous tissues were collected.The expressions of SKA3 and DUSP26 in these tissues were assessed using immunohistochemistry, and their correlations with clinicopathological characteristics were analyzed.The relationship between SKA3 and DUSP26 in cancer tissues was examined using the Spearman correlation coefficient.After one year of follow-up, the association between SKA3 and DUSP26 expressions in cancer tissues and patient prognosis was evaluated using Kaplan-Meier curves, and prognostic factors were analyzed using the Cox proportional hazards model.Results:In this cohort of 145 elderly patients aged 65 to 85 years(mean age: 72.61±3.87), including 91 males, we observed that the positive expression rates of SKA3 and DUSP26 in cancer tissues were 66.21%(96/145)and 71.03%(103/145), respectively.These rates were significantly higher than those found in para-carcinoma tissues, which were 16.55%(24/145)and 13.79%(20/145), with a P-value of <0.05.Spearman correlation analysis revealed a positive correlation between SKA3 and DUSP26 expression in cancer tissues( r=0.571, P<0.001).Moreover, the proportions of low differentiation, clinical staging at stages Ⅰ-Ⅱ, and lymph node metastasis were significantly higher in the SKA3-positive group compared to the SKA3-negative group( P<0.05), and similarly, these proportions were higher in the DUSP26-positive group than in the DUSP26-negative group( P<0.05).Kaplan-Meier survival analysis indicated that after one year of follow-up, the cumulative survival rates for patients with positive expressions of SKA3 and DUSP26 were 61.46%(59/96)and 58.25%(60/103), respectively, which were significantly lower than those with negative expressions[87.76%(43/49)and 92.86%(39/42), P<0.05].Cox regression analysis identified low differentiation( HR=1.817, 95% CI: 1.294-2.550), clinical staging at stage Ⅲ( HR=1.939, 95% CI: 1.315-2.858), lymph node metastasis( HR=1.898, 95% CI: 1.350-2.670), as well as positive expressions of SKA3( HR=2.071, 95% CI: 1.317-3.257)and DUSP26( HR=2.136, 95% CI: 1.402-3.256)as significant risk factors for prognosis( P<0.05). Conclusions:The expression rates of SKA3 and DUSP26 in cancer tissues are significantly elevated in elderly patients with NSCLC.Furthermore, these two biomarkers are correlated with the degree of differentiation, clinical staging, and lymph node metastasis, indicating their potential utility in evaluating the prognosis of elderly NSCLC patients.

Under the Healthy China strategy, the training of preventive medicine professionals should conform to the development of the times and the needs of public health. The article analyzed the problem of "disconnection between medical care and prevention" in teaching the course of Obstetrics and Gynecology for students majoring in preventive medicine, and proposed to strengthen the strategy of "integration of medical care and prevention". Guided by the concepts of "Comprehensive Health", with the cornerstone of cultivating morality and talents, the reform focused on enhancing the post competency of preventive medicine talents. Course content was optimized by reinforcing prevention-focused elements, student-centered teaching method innovation was advocated, and simulation-based training teaching system was established. Moreover, projects integrating science and education were used to improve faculty teaching capacity with tiered and diversified approaches. Course assessment methods were revised and "ideological and political education" was incorporated to establish the education concept of "emphasis on prevention and integration of medical care and prevention". The survey showed that these reform measures effectively improved the comprehensive clinical literacy of preventive medicine students in obstetrics and gynecology, which is of great significance for building a "integration of medical care and prevention" public health talent training model. In the future, the long-term effectiveness of course reform will be ensured from the perspectives of teaching resources, personnel investment, and policy support.

Objective:To report a case of hereditary fibrosing poikiloderma with tendon contracture, myopathy, and pulmonary fibrosis (POIKTMP), and analyze the genotype-phenotype correlation through a literature review.Methods:The clinical manifestations and genetic testing results of a Chinese Han child with POIKTMP were reported. Relevant literature was searched in databases using ′FAM111B gene′, ′hereditary fibrosing poikiloderma with tendon contracture, myopathy, and pulmonary fibrosis′ or ′POIKTMP′ as keywords, and the clinical manifestations, mutation sites of the FAM111B gene, and the correlation between them were statistically analyzed.Results:A 6.5-year-old girl developed POIKTMP at 6 months of age. Dermatological examination showed irregular brown patches and dotted hypopigmentation on the face and neck, mainly on the forehead and around the mouth, telangiectasia on the cheeks and nose, pigmentation and hypopigmentation on the limbs and trunk, as well as sparse, pale eyebrows. A total of 39 cases of POIKTMP were retrieved, including this case, all of which had clinical data and were definitively diagnosed. Fourteen variants of the FAM111B gene had been reported, including 1 in-frame deletion variant and 13 missense variants. Among the 39 cases, the incidence of poikiloderma/photosensitivity/facial erythema/telangiectasia was 100% (39/39), alopecia was 87.2% (34/39), and that of hypohidrosis/heat intolerance was 82.1% (32/39). The incidence of extracutaneous manifestations was as follows: tendon contractures/digital sclerosis, 69.2% (27/39) ; elevated liver transaminases, 46.2% (18/39) ; muscle pain/weakness/amyotrophy, 43.6% (17/39). The incidence of eczema-like lesions, bullous lesions, and elevated liver transaminases was significantly higher in the young versus the adult group ( P < 0.05) . Conclusions:This case of POIKTMP was characterized by brown patches, hypopigmentation, and sparse eyebrows. POIKTMP is a progressive multisystem disorder with age-related clinical manifestations. Early genetic testing is crucial for evaluating potential complications and providing genetic counseling.

Objective:To evaluate the diagnostic value of MRI findings in differentiating between tophus and giant cell tumors of the tendon sheath (GCTTS) in the knee.Methods:The study was a case-control study. The clinical and MRI data of patients diagnosed with knee tophus or GCTTS was retrospectively analyzed at the Affiliated Hospital of Qingdao University from September 2018 to September 2024. The study included 23 cases of tophus and 22 cases of GCTTS. MRI sequences, including T 1WI, fat-suppressed T 2WI, and proton density weighted imaging, were evaluated. Parameters including lesion signal intensity and homogeneity, margin, maximum diameter, location (inside or outside the synovial cavity), ligament/tendon involvement, ligament/tendon parenchymal changes, adjacent bone erosion, bone marrow edema, synovial hyperplasia, joint effusion, and periarticular soft tissue swelling were recorded. Independent sample t-tests, χ2 tests, or Fisher exact tests were used to compare MRI findings between the two groups. Multivariate logistic regression was performed to identify independent predictive factors. Results:Significant differences in terms of maximum diameter, location (inside or outside the synovial cavity), ligament/tendon involvement, ligament/tendon parenchymal changes, adjacent bone erosion, bone marrow edema, and periarticular soft tissue swelling between the two groups were found (all P<0.05). No significant differences for other parameters were observed (all P>0.05). Lesion location and ligament/tendon parenchymal involvement demonstrated the highest sensitivity and specificity for distinguishing the two diseases. The sensitivity and specificity values for lesion location were 0.78 and 0.95. The sensitivity and specificity values for ligament/tendon involvement were 0.78 and 1.00. Multivariate logistic regression identified lesion location (inside or outside the synovial cavity) as an independent predictor for differentiating tophus from GCTTS ( OR=31.48, 95% CI 1.58-625.69, P=0.024). Conclusion:The location of the lesion (inside or outside the synovial cavity) and involvement of ligament/tendon parenchyma are critical factors in differentiating knee tophus from GCTTS. Additionally, lesion location serves as an independent predictor for distinguishing between the two conditions.

BACKGROUND: Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets. METHODS: In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45 + BM cells were enriched with human CD45 microbeads. The CD45 + cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis. RESULTS: In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment. CONCLUSIONS This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.
Humans ; Lymphoma, Large B-Cell, Diffuse/therapy* ; Tumor Microenvironment/genetics* ; Antigens, CD19/metabolism* ; Leukemia, Myelomonocytic, Chronic/genetics* ; Immunotherapy, Adoptive/adverse effects* ; Male ; Single-Cell Analysis/methods* ; Female ; Sequence Analysis, RNA/methods* ; Receptors, Chimeric Antigen ; Middle Aged

Objective:To report a case of hereditary fibrosing poikiloderma with tendon contracture, myopathy, and pulmonary fibrosis (POIKTMP), and analyze the genotype-phenotype correlation through a literature review.Methods:The clinical manifestations and genetic testing results of a Chinese Han child with POIKTMP were reported. Relevant literature was searched in databases using ′FAM111B gene′, ′hereditary fibrosing poikiloderma with tendon contracture, myopathy, and pulmonary fibrosis′ or ′POIKTMP′ as keywords, and the clinical manifestations, mutation sites of the FAM111B gene, and the correlation between them were statistically analyzed.Results:A 6.5-year-old girl developed POIKTMP at 6 months of age. Dermatological examination showed irregular brown patches and dotted hypopigmentation on the face and neck, mainly on the forehead and around the mouth, telangiectasia on the cheeks and nose, pigmentation and hypopigmentation on the limbs and trunk, as well as sparse, pale eyebrows. A total of 39 cases of POIKTMP were retrieved, including this case, all of which had clinical data and were definitively diagnosed. Fourteen variants of the FAM111B gene had been reported, including 1 in-frame deletion variant and 13 missense variants. Among the 39 cases, the incidence of poikiloderma/photosensitivity/facial erythema/telangiectasia was 100% (39/39), alopecia was 87.2% (34/39), and that of hypohidrosis/heat intolerance was 82.1% (32/39). The incidence of extracutaneous manifestations was as follows: tendon contractures/digital sclerosis, 69.2% (27/39) ; elevated liver transaminases, 46.2% (18/39) ; muscle pain/weakness/amyotrophy, 43.6% (17/39). The incidence of eczema-like lesions, bullous lesions, and elevated liver transaminases was significantly higher in the young versus the adult group ( P < 0.05) . Conclusions:This case of POIKTMP was characterized by brown patches, hypopigmentation, and sparse eyebrows. POIKTMP is a progressive multisystem disorder with age-related clinical manifestations. Early genetic testing is crucial for evaluating potential complications and providing genetic counseling.