To establish a morphologic classification system for characterizing blast cells in patients with acute promyelocytic leukemia (APL) and analyze the correlation of different APL morphologic characteristics with conventional tests and genetic variants.

To analyze the clinical characteristics and prognosis of patients with co-mutation of CEBPA gene and GATA2 gene, so as to facilitate clinicians to formulate more accurate individualized treatment plans for patients.

To analyze the immune-related core genes differentially expressed in oral squamous cell carcinoma(OSCC) and construct an immune-related prognostic risk model for OSCC patients.

Peutz-Jeghers syndrome (PJS) is an autosomal dominant genetic disorder characterized by mucocutaneous pigmentation and multiple hamartomatous polyps, which leads to an increased susceptibility to tumors. The clinical incidence is rare, and the only currently identified pathogenic gene is the serine/threonine kinase 11/liver kinase B1 (STK11/LKB1) located on the short arm of chromosome 19 (19p13.3). This condition can lead to various complications, such as gastrointestinal bleeding, intussusception, intestinal obstruction, and malignancy. In childhood, the greatest risk is associated with intussusception, which increases the risk of surgical intervention and significantly impacts the growth, development, and quality of life of the children. This article provides an overview of the current research status regarding the clinical characteristics, etiology, pathogenesis, diagnosis, and treatment of PJS in children.

Objective: To analyze the clinical characteristics and prognostic factors of non-small cell lung cancer (NSCLC) patients with sensitive epidermal growth factor receptor (EGFR) mutations who developed small cell lung cancer (SCLC) transformation after treatment with EGFR tyrosine kinase inhibitors (TKI). Methods: We conducted a retrospective collection of clinical data for 21 patients with advanced EGFR mutant NSCLC who developed SCLC transformation after EGFR-TKI treatment at Beijing Chest Hospital, Capital Medical University from January 2015 to December 2021. The clinical characteristics were summarized and the prognosis analysis was conducted. Patients were followed up until February 2024. The efficacy was evaluated using Solid Tumor Response Evaluation Criteria, and survival curves were plotted using the Kaplan-Meier method, and the log-rank test was used to compare the differences in survival time (OS) between limited stage and extensive stage in transformed SCLC patients. Cox proportional hazards model was used to analyze the influencing factors of survival after SCLC transformation. Results: Among the 21 patients, there were 5 males and 16 females, with an age range of 33-74 years old [(58.9±2.6) years old]. All 21 patients were adenocarcinoma with sensitive EGFR mutations. There were 18 cases (85.7%) with EGFR gene 19del mutation, including 1 case of 19del+anaplastic lymphoma kinase (ALK) mutation, and 3 cases of L858R mutation. Among the transformed SCLC, there were 11 cases of pure SCLC and 10 cases of mixed SCLC (coexisting of adenocarcinoma and small cell carcinoma components). The median time from diagnosis of NSCLC to SCLC transformation was 12.0 months (95%CI: 7.6-16.3 months). Among the 21 cases of SCLC transformation, there were 13 cases with the extensive stage and 8 cases with the limited stage. Among them, 16 patients received systemic chemotherapy based on etoposide, of which 13 cases could be evaluated for efficacy, 11 cases could be calculated for PFS. Five cases had partial remission, 5 cases were stable, 3 cases had disease progression, and 3 cases cloud not be evaluated. The median progression free survival time (PFS) was 4.8 months (95%CI: 2.8-6.8 months). The median survival time (OS) after SCLC transformation in 21 patients was 10.6 months (95%CI: 7.0-14.2 months), with a median OS of 8.8 months (95%CI: 6.3-11.4 months) for patients with the extensive stage and 27.5 months (95%CI: 9.6-34.4 months) for patients with the limited stage, with statistically significant differences (P=0.002). Cox proportional hazards model analysis showed that the limited stage after SCLC transformation was a protective factor for OS (HR=0.32, 95%CI: 0.12-0.73, P=0.010). The median OS of 21 patients from the diagnosis of lung cancer was 24.9 months (95%CI: 13.0-36.7 months). Conclusions: NSCLC patients with SCLC transformation are all adenocarcinomas, and the proportion of EGFR19del mutations is relatively high. After SCLC transformation, the standard chemotherapy regimen for SCLC is generally used for treatment. The OS after SCLC transformation is related to the stage, and the prognosis is better in the limited stage.

Objective To screen for the key genes involved in the development of ovarian cancer (OV), analyze the immune cell infiltration and construct a risk model, so as to provide evidence for the early diagnosis, treatment and prognosis evaluation of OV patients. Methods The GSE18520 and GSE6008 datasets were analyzed for differentially expressed genes (DEGs) using the GEO2R data analysis tool, and a Venn diagram was generated. Then, DEGs were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and protein-protein interaction (PPI) networks, as well as mutations, expression and prognosis analysis to identify key genes. Next, a risk model was constructed and immune cell infiltration analysis of key genes was performed. Finally, ovarian cancer tissues were collected as the experimental group, and adjacent normal tissues were collected as the control group. The expression of claudin 4 (CLDN4) mRNA and protein levels were detected using real-time quantitative PCR (RT-qPCR) and Western-blot, and the results were compared between the two groups. Results CLDN4 was identified as a key gene in the development of OV. As its expression increased, the prognosis risk of OV patients worsened, which unfavorably impacted their overall survival (OS). A significant positive correlation was found between CLDN4 and dendritic cell (DC) in the OV microenvironment, and high expression of DCs was significantly associated with better OS in OV patients. The mRNA and protein expression levels of CLDN4 were significantly increased in OV tissues, with statistically significant differences. Conclusion CLDN4 is a key gene in the development of OV, and may serve as a potential biomarker and immunotherapy target for OV.

Objective To investigate the impact of dipeptidyl peptidase 3 (DPP3) on the immune escape of gastric cancer cells by regulating the expression of major histocompatibility complex class I chain-related gene B (MICB). Methods Knocking down DPP3 in MKN-45 human gastric cancer cells and overexpressing DPP3 in MGC-803 human gastric cancer cells, observing changes in cell proliferation, migration ability, and responses to natural killer (NK) cell cytotoxicity; using whole-transcriptome sequencing to identify the MICB gene, and knocking down MICB in DPP3-overexpressing cells to verify changes in cellular behavior. In C57 mice, the in vivo tumorigenic ability of DPP3-knockout cells and the infiltration of CD56+ cells in tissues were examined. Results Knocking out DPP3 promoted the proliferation and migration of gastric cancer cells, reduced MICB expression, and made the cells less sensitive to NK cell cytotoxicity; the tumorigenic ability in mice increased and CD56+ cells tissue infiltration decreased by DPP3 knocking out in the gastric cancer cells, but DPP3 overexpression showed the opposite results. Knocking down MICB could reverse the phenotypic changes induced by high DPP3 expression. Conclusion DPP3 inhibits the immune escape of gastric cancer cells by downregulating MICB expression.

Objective To explore the impact of M2 macrophages on the malignant biological behavior of esophageal cancer by inhibiting the anti-tumor ability of CD8+ T cells. Methods Using phorbol myristate acetate (PMA) combined with interleukin 4 (IL-4)/IL-13, we induced human monocytic leukemia cells (THP-1) to become M2 macrophages and the detected related inflammatory factors by real-time quantitative PCR. We used magnetic bead sorting to isolate CD8+ T cells from healthy volunteers' peripheral blood, and verified the purity of the sorted cells by flow cytometry. We established a non-contact co-culture system between CD8+ T cells and esophageal squamous carcinoma cells (CD8+ T cell), and established a non-contact co-culture system between M2 macrophages, CD8+ T cells, and esophageal squamous carcinoma cells (M2 macrophages combined with CD8+ T cell). The plate clone formation assay and CCK-8 cell toxicity assay were used to detect the proliferation ability of tumor cells in each group. The TranswellTM assay was used to detect the invasive and migratory abilities of tumor cells in each group. Flow cytometry was used to detect and analyze the apoptosis of tumor cells in each group. GraphPadPrism9.5 software was used for statistical analysis and graphing. Results After induction, the expression of IL-10 and arginase 1 (Arg1) in macrophages was upregulated, while the expression of IL-12 and tumor necrosis factor-alpha (TNF-α) was downregulated, showing the characteristics of M2 macrophages. Peripheral blood CD8+ T cells were successfully selected by magnetic bead sorting, with a positive rate of over 90%. The proliferation, invasion, migration and anti-apoptosis ability of esophageal squamous carcinoma cells co-cultured with CD8+ T cells in the non-contact manner were significantly lower than those of the single cancer cell group; while the proliferation, invasion, migration and the anti-apoptosis ability of esophageal squamous carcinoma cells co-cultured with CD8+ T cells pretreated with M2 macrophage conditioned medium were significantly enhanced compared with those of esophageal squamous carcinoma and CD8+ T cells co-cultured group. Conclusion M2 macrophages promote the proliferation, invasion, migration, and anti-apoptosis of esophageal cancer cells by inhibiting the anti-tumor ability of CD8+ T cells.

Objective To investigate the immunomodulatory effects of CXCL8 on the microenvironment in colorectal cancer (CRC). Methods Subcutaneous transplanted tumor model in BALB/c mice was established using CXCL8-overexpressing CT26, a murine CRC cell line . Tumor growth was monitored, and after three weeks of formation, the tumors were excised, and the spleens were harvested. Firstly, the tumor single-cell suspensions were prepared, and the infiltration of M2 macrophages and CD8+ T cells in the tumor microenvironment were detected by flow cytometry. Additionally, the spleen single-cell suspensions were prepared and CD8+ T cells were sorted. T cells were co-cultured with CXCL8-overexpressing CT26 cells in vitro, and the cytotoxicity assays were performed to evaluate the killing ability of T cells. Results Overexpression of CXCL8 promoted the growth of CRC transplanted tumors. Tumor overexpressing CXCL8 exhibited increased the infiltration of M2 macrophages and decreased the infiltration of CD8+ T cells. However, overexpression of CXCL8 in CRC cells did not affect the cytotoxicity of CD8+ T cells in vitro. Conclusion CXCL8-overexpressing CRC cells promoted the infiltration of M2 macrophages and inhibited CD8+ T cell infiltration to generate an immunosuppressive microenvironment in CRC.

To explore the role and clinical significance of cell-cycle dependent kinase 1 (CDK1) and its upstream and downstream molecules in the development of malignant peripheral nerve sheath tumor (MPNST) through the analysis of clinical tissue samples.

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disease caused by mutations in the NF1 gene. The disease is characterized by neurofibromatosis, which simultaneously affects multiple systems such as nerves, skin, and bone, and has complex clinical manifestations. Since the National Institutes of Health (NIH) established diagnostic criteria in 1988, the diagnosis and treatment of NF1 have progressed significantly. However, due to the complexity of the disease and the lack of effective treatments, the diagnosis and treatment of NF1 still face many challenges. Strengthening multidisciplinary collaboration, improving and popularizing disease diagnosis and treatment strategies, and developing more effective drugs and treatment methods are the keys to further improve the treatment level of NF1 diseases.

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disease caused by the mutations in the NF1 gene, with an incidence of approximately 1/3 000. Affecting multiple organs and systems throughout the body, NF1 caused a wide variety of clinical symptoms. A comprehensive multidisciplinary diagnostic and treatment model is needed to meet the diverse needs of NF1 patients and improve their quality of life. In recent years, the emergence of targeted therapies has further benefited NF1 patients, and the number of clinical consultations has increased dramatically. However, due to the rarity of the disease itself and insufficient attention previously, the standardized, systematic, and precise diagnosis and treatment model of NF1 still needs to be further improved. In this paper, we reviewed the current status of comprehensive diagnosis and treatment of NF1 in China, combine with our long-term experiences in diagnosis and treatment of this disease. Meanwhile, we propose future directions and several suggestions for the comprehensive diagnosis and treatment model for Chinese NF1 patients.

Lymphomas are a highly heterogeneous group of tumors that are classified into several subtypes. The gold standard method for the molecular profiling of lymphoma is based on invasive lymph node or tissue biopsy. However, this method cannot accurately capture spatial tumor heterogeneity in each patient as well as systemic tumor invasion and tumor burden. Circulating tumor DNA (ctDNA) is an emerging and highly versatile biomarker that overcomes the basic limitations of imaging scanning and tissue biopsy; has the characteristics of being simple, rapid, and non-invasive; and has good specificity and high sensitivity. ctDNA testing has been applied to a variety of subtypes of lymphoma and has been used for somatic mutation genotyping, efficacy monitoring during treatment, detection of minimal residual disease, and the prediction of survival, which may help clinicians make better clinical decisions in the diagnosis and treatment of lymphoma patients. Furthermore, this study also aims to review the different methods of ctDNA analysis and describe the specific applications of ctDNA in different lymphoma subtypes.

Refractory acute T-lymphoblastic leukemia (T-ALL), which is characterized by a low sensitivity to conventional induction therapy and poor prognosis, poses significant challenges during treatment. This study reported a case of refractory T-ALL patient with mutations in the JAK1, JAK3, and STAT5B genes from Nanjing University's Gulou Hospital. Following an unsuccessful course of standard VDLP regimen chemotherapy, the treatment was modified to include ruxolitinib in combination with venetoclax and azacitidine. Subsequent to this therapy, the patient achieved bone marrow minimal residual disease (MRD) negativity. Notably, pleural effusion and mediastinal mass significantly improved the post-chest cavity infusion of dexamethasone combined with etoposide at the same stage. The patient also underwent allogeneic hematopoietic stem cell transplantation upon achieving bone marrow remission and was followed up until January 2024. Ruxolitinib combined with venetoclax and azacytidine has shown promising efficacy and safety in treating refractory T-ALL harboring the JAK1, JAK3, and STAT5B mutations, providing a novel therapeutic approach for such patients.

A retrospective analysis of the clinical data of seven acute B-lymphoblastic leukemia (B-ALL) patients with TCF3-HLF fusion gene-positive admitted to the First Affiliated Hospital of Soochow University from June 2017 to August 2022 was conducted to summarize their clinical features and prognoses. The seven B-ALL patients comprised four males and three females, with a median age of 18 (11-33) years. Five patients tested positive for CD33 expression, and four patients had a normal karyotype. Two patients had hypercalcemia at the initial diagnosis, and one patient developed hypercalcemia at relapse. Six patients presented with coagulation dysfunction at diagnosis. After induction chemotherapy, five out of seven patients achieved complete remission, of which four subsequently relapsed. Two patients did not achieve remission even after two rounds of induction chemotherapy, with one achieving complete remission after treatment with blinatumomab immunotherapy. Three patients underwent chimeric antigen receptor T cell therapy, whereas three patients subsequently underwent hematopoietic stem cell transplantation. Five patients died, while two patients survived with sustained complete remission. TCF3-HLF-positive B-ALL is rare and has a high relapse rate and poor prognosis.

Variant acute promyelocytic leukemia (APL) and APL-like leukemia are rare types of APL, with t (16;17) chromosome abnormality being even rarer. An APL-like patient with t (16;17) chromosome abnormality, which was characterized by bone, lymph node, and central nervous system involvement, was admitted to our hospital. He achieved complete remission after several cycles of chemotherapy and subsequently underwent hematopoietic stem cell transplantation. Furthermore, the diagnosis and treatment of this patient were reported and a literature review was conducted.

Objective: To investigate the clinicopathological features and genetic mutation status of pulmonary intravascular large B cell lymphoma. Methods: The clinicopathological data of eight patients diagnosed with pulmonary intravascular large B cell lymphoma, from April 2018 to May 2023, were retrospectively analyzed. The genetic profile of six patients was detected via next-generation sequencing (NGS) and followed up. Results: All patients included one male and seven females, with a median age of 64 years (ranging from 45 to 66 years). Respiratory symptoms were the most common (7 cases), B symptoms in two cases, hemophagocytic syndrome in two cases. Multiple diffuse ground-glass opacities in both lungs were observed based on the high-resolution chest CT scan. Six cases of mild to moderate ventilation or diffusion dysfunction were observed based on the pulmonary function tests. Moreover, two cases of hypoxemia and two cases with type Ⅰ respiratory failure were recorded. The serum lactate dehydrogenase level increased (7/8), β2-MG level increased (2/8), neuron-specific enolase level increased (7/8), total number of peripheral blood lymphocytes decreased (7/8), and clinical stages were all stage Ⅳ. The neoplastic lymphoid cells were lodged in the lumina of venules and capillaries of the alveolar septum; the tumor cells were large, with prominent nucleoli and frequent mitotic figures. The malignant cells were detected in the extravascular surrounding lung tissue in all cases. The tumor cells expressed mature B cell-associated antigens CD20 and CD79a, and the vascular endothelial markers CD31 and CD34 showed that the tumor cells were filled in the blood vessels, infiltrated blood vessel walls, and perivascular areas. One case was germinal center-type, seven cases were non-germinal center-type, two cases were double-expressing lymphoma, and all cases were EBER-negative. Furthermore, the top five genes with mutation frequencies detected by NGS were MYD88 (5/6), PIM1 (5/6), CD79B (4/6), TCF3 (4/6), and TP53 (3/6). Of the eight cases, seven patients received R-CHOP-based chemotherapy, six cases had complete remission after chemotherapy, one case died, and one case was lost to follow-up. Conclusions: Pulmonary vascular large B cell lymphoma is rare, which shares similar patterns with interstitial lung disease on imaging. Transbronchial lung biopsy is an effective method to confirm the diagnosis. Immunochemotherapy with BTK inhibitors can provide a survival advantage for patients in the future based on molecular typing.

Objective: To explore the role of tumor necrosis factor receptor-associated factor 4 (TRAF4) in promoting the abnormal activation of epidermal growth factor receptor (EGFR) and its effect on lung cancer cell proliferation, migration and invasion. Methods: Tumor tissues from patients who underwent lung adenocarcinoma resection at The First Affiliated Hospital of Second Military Medical University, from January 2015 to May 2017 were collected, and the expressions of TRAF4 and Ki-67 in lung cancer tissues were detected by immunohistochemistry, the mRNA levels of Cyclin D and Vimentin were detected by real-time fluorescence quantitative PCR (qRT-PCR). The effect of TRAF4 on the tumor growth ability of lung cancer A549 cells was investigated by the xenograft model, the effect of TRAF4 or EGFR on the tumor proliferation ability was detected by using cell counting kit 8 (CCK8) and BrdU assay, and the migration and invasion abilities of tumor cells were detected by Transwell assay. Different structural domain deletion expression vectors of TRAF4 and EGFR were constructed to transfect cells, and the interaction mode of TRAF4 and EGFR was investigated by immunoprecipitation assay. Results: The expression of TRAF4 in non-small cell lung cancer (NSCLC) tissues was positively correlated with the expressions of Ki-67, cyclin D, and vimentin (r2: 0.438, 0.695, and 0.736, respectively, all P＜0.01). Immunohistochemical assay of tumor tissues from NSCLC patients showed that tissues with high expression of TRAF4 were also high in Ki-67. Patients with high TRAF4 expression (TRAF4 positivity >30%) had a shorter progression-free survival (PFS) time than that of patients with low TRAF4 expression (TRAF4 positivity ≤30%) (median PFS of 12 and 19 months, respectively; P=0.034). Traf4-/- cells had a weakened proliferative capacity than traf4+/+ cells and formed tumors with smaller size (P＜0.05). The expression level of Ki-67 in the tumor tissues formed by traf4-/- cells [(45.6±8.7)%] was lower than that in the tumor tissues formed by traf4+/+ cells [(62.3±10.3)%, P=0.015], the mRNA levels of cyclin D (1.01±0.15) and vimentin (1.01±0.12) in the traf4-/- cells were lower than those of the traf4+/+ cells (3.41±0.32 and 3.12±0.18, respectively, both P＜0.05).The western blot results showed that, with the elevated intracellular expression level of TRAF4, phosphorylation level of EGFR was significantly increased in both wild-type EGFR and activation mutant EGFR-expression cells. The capacities of proliferation, migration and invasion of A549 cells was weakened after EGFR knockdown (all P＜0.01). Immunoprecipitation experiments showed that TRAF4 binds to the peptide segment of the near-membrane region of EGFR through the TRAF structural domain, and the mutual binding between EGFR molecules was enhanced under TRAF4 overexpression conditions. Increasing TRAF4 expression promoted EGFR molecular phosphorylation and activation of downstream signaling. Conclusions: TRAF4 expression is elevated in NSCLC tissues and tumor cells, which promotes tumor proliferation, migration and invasion. TRAF4 directly binds to EGFR molecules, enhances its own phosphorylation and activates the downstream signaling pathway by promoting the interaction between EGFR molecules.

The global aging population is leading to an increasing incidence of cancer, exacerbating the global burden of cancer. By 2040, the total number of cancer patients worldwide is projected to reach 28 million. With advancements in tumor molecular biology research and the widespread application of next-generation sequencing technology, precision treatment for cancer has made significant progress in clinical settings. Selective targeting of the Braf gene has emerged as one of the early successful cases of precision medicine for tumors. Braf gene mutations can result in unrestricted activation of downstream kinases in the mitogen-activated protein kinase (MAPK) cell signaling pathway, promoting rapid proliferation of tumor cells. BRAF inhibitors, either as monotherapy or in combination with MEK inhibitor, have been approved for various cancers, including melanoma, non-small cell lung cancer, thyroid cancer, colorectal cancer and glioma, among others. Clinical studies related to BRAF inhibitors are continuously exploring new applications. However, there is currently no consensus on the use of BRAF inhibitors in the diagnosis and treatment of multiple solid cancers in China. This article integrates clinical evidence of Braf mutations in multiple solid cancers to establish an expert consensus on the diagnosis and treatment of malignant solid cancers with Braf gene mutations. The goal is to promote and guide the standardized application of BRAF inhibitors.

Objective: To explore the detection of BRAF, RAS, TERT promoter, and TP53 gene mutations in solitary thyroid micronodule (TMN) specimens obtained by ultrasound-guided fine-needle aspiration (US-FNA) using next-generation sequencing (NGS) technology and assess its diagnostic value in thyroid microcarcinomas (TMC). Methods: On-site recruitment of 428 patients with single suspicious TMC who underwent thyroid ultrasound examination, US-FNA, and NGS from September 2018 to July 2021 at Beijing Tongren Hospital affiliated to Capital Medical University. A total of 147 patients were finally included. NGS was used to detect mutations in the BRAF, RAS, TERT promoter, and TP53 genes in the US-FNA specimens. Comparisons were made between patients with and without gene mutations in terms of age, gender, and the maximum diameter of nodules. The diagnostic efficiency of BRAF mutation for TMC was calculated using the receiver operating characteristic (ROC) curve, with postoperative pathology as the gold standard. Results: The age [M (Q1, Q3)] of the 147 patients was 43.0 (32.0, 51.0) years, and 37 were male (25.2%). Among the 147 US-FNA specimens, 97 (66.0%) were detected with BRAF gene mutations, all of which were p.V600E point mutation; 6 (4.1%) were detected with RAS gene mutation, and no TERT promoter or TP53 gene mutations were detected. Postoperative pathology confirmed that 136 cases were TMC, all of which were papillary thyroid microcarcinomas (PTMC); 11 cases (7.5%)were benign. Among 136 TMC samples, BRAF gene mutations were detected in 97 cases (71.3%). There were no statistically significant differences in age, gender, and maximum nodule diameter between patients with and without BRAF gene mutations (all P>0.05). The sensitivity and specificity of BRAF gene mutation in diagnosing TMC were 71.3% and 100.0%, respectively, with an area under the ROC curve (AUC) (95%CI) of 0.857 (0.789-0.925). For nodules classified as Bethesda Ⅲ-Ⅴ, the sensitivity and specificity were 63.0% and 100.0%, respectively, with an AUC (95%CI) of 0.815 (0.680-0.950). Conclusions: NGS technology can successfully detect multiple gene mutations in US-FNA specimens from TMN patients, especially BRAF gene mutation, and BRAF gene mutation has certain value in diagnosing TMC.