Analysis of the resistance profile of real-world alectinib first-line therapy in patients with ALK rearrangement-positive advanced non-small cell lung cancer using organoid technology in one case of lung cancer.

Background: Alectinib has achieved excellent therapeutic efficacy in anaplastic lymphoma kinase (ALK) fusion gene-positive non-small cell lung cancer (NSCLC) patients, however, patients eventually develop resistance to it. Exploring the gene variant mapping after alectinib resistance provides a basis for the whole management of ALK-positive advanced NSCLC. This study aimed to characterize the mutation profiles of real-world ALK rearrangement-positive advanced NSCLC patients after first-line alectinib treatment resistance. The research also investigated the treatment options and coping strategies after resistance. Methods: Clinical data of patients with advanced NSCLC who received first-line alectinib treatment in the First Affiliated Hospital of Guangzhou Medical University between November 2018 and April 2022 were collected. Moreover, next-generation sequencing (NGS) data of the patient's baseline and post-resistance tissues were gathered. One patient underwent lung cancer organoid culture and drug sensitivity testing. Results: Out of 35 first-line alectinib-treated patients with advanced NSCLC, 31 are presently in progression-free survival (PFS; 4.3-35.0 months). Four patients experienced progressive disease, and all of them were sequentially treated with ceritinib. Tissue NGS results before sequential treatment in three patients indicated an echinoderm microtubule-associated protein-like 4-ALK fusion that remained at the original baseline, and the PFS for ceritinib treatment was 0.5-1.3 months. One patient developed acquired resistance mutations in the structural domain of ALK protein kinase (V1180L and E1161D), and the PFS for ceritinib treatment was 6.7 months. For one patient who maintained original baseline ALK rearrangement positive without acquired mutation after progression of ceritinib resistance, lung cancer-like organ culture with sequential brigatinib and lorlatinib led to a PFS of 3.2 and 1.9 months, respectively, which aligned with the corresponding drug susceptibility testing results for this patient. Conclusions: For ALK rearrangement-positive patients, blind sequencing of other second-generation tyrosine kinase inhibitors (TKIs) or third-generation lorlatinib may not guarantee satisfactory tumor suppression following first-line second-generation ALK-TKI alectinib administration for treatment progression. NGS testing of patients' blood or tissue samples after disease progression may provide insight into the etiology of alectinib resistance. Patient-sourced drug sensitivity testing of lung cancer-like organs selects drug-sensitive medications based on NGS results and provides a reference for subsequent drug therapy for patients after drug resistance, particularly those who remain ALK rearrangement-positive at baseline.

The prognostic impact of severe grade immune checkpoint inhibitor related pneumonitis in non-small cell lung cancer patients.

Objective: To compare the prognostic differences between non-small cell lung cancer (NSCLC) patients with mild and severe checkpoint inhibitor-associated pneumonitis (CIP), and explore the causes of death and prognostic risk factors in NSCLC patients with severe CIP. Methods: A retrospective study of a cohort of 116 patients with unresectable stage III or IV NSCLC with any grade CIP from April 2016 to August 2022 were conducted. To analyze the clinical characteristics of patients with different CIP grades, patients were divided into mild CIP group (grade 1-2, n=49) and severe CIP group (grade 3-5, n=67) according to the grade of CIP. To explore the OS-related risk factors in the severe CIP group, the patients were divided into a good prognosis (GP) group (≥ median OS, n=30) and a poor prognosis (PP) group (< median OS, n=37) based on whether their overall survival (OS) were greater than median OS. Baseline clinical and laboratory data were collected for analysis. Results: The median OS of all NSCLC patients combined with CIP was 11.4 months (95%CI, 8.070-16.100), The median OS for mild CIP and severe CIP was 22.1 months and 4.4 months respectively (HR=3.076, 95%CI, 1.904-4.970, P<0.0001). The results showed that the most common cause of death among severe CIP patients in the PP group was CIP and the most common cause in the GP group was tumor. The univariate regression analysis showed that suspension of antitumor therapy was a risk factor for poor prognosis (OR=3.598, 95%CI, 1.307-9.905, p=0.013). The multivariate logistic regression analysis showed that suspension of anti-tumor therapy (OR=4.24, 95%CI, 1.067-16.915, p=0.040) and elevated KL-6 (OR=1.002, 95%CI, 1.001-1.002, p<0.001) were independent risk factors for poor prognosis. Conclusion: In conclusion, patients with severe CIP had a poor prognosis, especially those with elevated KL-6, and the main cause of death is immune checkpoint inhibitor-associated pneumonitis complicated with infection. In addition, anti-tumor therapy for severe CIP patients should be resumed in time and should not be delayed for too long.

Cancer marker TNFRSF1A: From single­cell heterogeneity of renal cell carcinoma to functional validation.

During the progression of renal cell carcinoma (RCC), tumor growth, metastasis and treatment response heterogeneity are regulated by both the tumor itself and the tumor microenvironment (TME). The aim of the present study was to investigate the role of the TME in RCC and construct a crosstalk network for clear cell RCC (ccRCC). An additional aim was to evaluate whether TNF receptor superfamily member 1A (TNFRSF1A) is a potential therapeutic target for ccRCC. Single-cell data analysis of RCC was performed using the GSE152938 dataset, focusing on key cellular components and their involvement in the ccRCC TME. Additionally, cell-cell communication was analyzed to elucidate the complex network of the ccRCC microenvironment. Analyses of data from The Cancer Genome Atlas and Clinical Proteomic Tumor Analysis Consortium databases were performed to further mine the key TNF receptor genes, with a particular focus on the prediction and assessment of the cancer-associated features of TNFRSF1A. In addition, following the silencing of TNFRSF1A using small interfering RNA in the 786-O ccRCC cell line, a number of in vitro experiments were conducted to further investigate the cancer-promoting characteristics of TNFRSF1A. These included 5-ethynyl-2'-deoxyuridine incorporation, Cell Counting Kit-8, colony formation, Transwell, cell cycle and apoptosis assays. The TNF signaling pathway was found to have a critical role in the development of ccRCC. Based on the specific crosstalk identified between TNF and TNFRSF1A, the communication of this signaling pathway within the TME was elucidated. The results of the cellular phenotype experiments indicated that TNFRSF1A promotes the proliferation, migration and invasion of ccRCC cells. Consequently, it is proposed that targeting TNFRSF1A may disrupt tumor progression and serve as a therapeutic strategy. In conclusion, by understanding the TME and identifying significant crosstalk within the TNF signaling pathway, the potential of TNFRSF1A as a therapeutic target is highlighted. This may facilitate an advance in precision medicine and improve the prognosis for patients with RCC.

Elemene Injection Overcomes Paclitaxel Resistance in Breast Cancer through AR/RUNX1 Signal: Network Pharmacology and Experimental Validation.

BACKGROUND: Paclitaxel (PTX) is a cornerstone chemotherapy for Breast Cancer (BC), yet its impact is limited by emerging resistance. Elemene Injection (EI) has shown potential in overcoming chemotherapy resistance. However, the efficacy by which EI restores PTX sensitivity in BC and the implicated molecular mechanism remain uncharted. METHODS: Network pharmacology and bioinformatic analysis were conducted to investigate the targets and mechanisms of EI in overcoming PTX resistance. A paclitaxel-resistant MCF-7 cell line (MCF-7PR) was established. The efficacy of EI and/or PTX in inhibiting cell viability was evaluated using sulforhodamine B assay, while cell proliferation was assessed using EdU staining. Furthermore, protein and gene expression analysis was performed through Western blotting and qPCR. RESULTS: The EI containing three active components exhibited a multifaceted impact by targeting an extensive repertoire of 122 potential molecular targets. By intersecting with 761 differentially expressed genes, we successfully identified 9 genes that displayed a direct association with resistance to PTX in BC, presenting promising potential as therapeutic targets for the EI to effectively counteract PTX resistance. Enrichment analysis indicated a significant correlation between these identified targets and critical biological processes, particularly DNA damage response and cell cycle regulation. This correlation was further substantiated through meticulous analysis of single-cell datasets. Molecular docking analysis revealed robust binding affinities between the active components of the EI and the identified molecular targets. Subsequently, in vitro experiments unequivocally demonstrated the dose- and time-dependent inhibitory effects of the EI on both PTX-resistant and sensitive BC cell lines, effectively mitigating the resistance phenotype associated with PTX administration. Furthermore, our findings have indicated EI to effectively suppress the protein expression levels of AR and RUNX1 in MCF-7 and MCF-7PR cells under PTX treatment, as well as downregulate the mRNA expression levels of stem-like properties' markers, KLF4 and OCT4, in these cell lines. CONCLUSION: Elemene Injection (EI) application has exhibited a significant capability to mitigate PTX resistance in BC, which has been achieved through targeted suppression of the AR/RUNX1 axis, revealing a key strategy to overcome chemotherapeutic resistance.

First case report of sunvozertinib for the treatment of HER2 exon 20 insertion in lung adenocarcinoma.

Human epidermal growth factor receptor 2 (HER2) is a transmembrane glycoprotein receptor with intracellular tyrosine kinase activity. It is generally considered as a poor prognostic marker. Targeted therapies, such as small molecule tyrosine kinase inhibitors (TKIs), showed limited efficacy in HER2-mutant advanced nonsmall cell lung cancer (NSCLC). In the 2023 National Comprehensive Cancer Network guidelines for NSCLC, antibody-drug conjugate trastuzumab emtansine is recommended for the treatment of HER2-mutant lung cancer. However, this medication is currently not approved in certain regions.So it is necessary to explore alternative treatment options for HER2-mutant NSCLC patients. In our study of a patient with HER2 exon 20 insertion lung adenocarcinoma who had previously failed multiple epidermal growth factor receptor (EGFR)-TKI treatments, we discovered that sunvozertinib could stabilize the patient's condition, achieving a progression-free survival of 87 days. This is a novel finding that may provide new treatment options for HER2 exon 20 insertion patients who have failed TKI therapy.

KIF23 promotes cervical cancer progression via inhibiting NLRP3-mediated pyroptosis.

BACKGROUND: Cervical cancer (CC), closely linked to persistent human papillomavirus infection, represents a major health problem for women worldwide. The objective of this study is to elucidate KIF23's role in the development of CC and its regulatory mechanism. METHODS: The bioinformatics methods were utilized to extract pyroptosis-associated differentially expressed genes (DEGs) and pivot genes from the GSE9750 and GSE63678 datasets, followed by immune infiltration analysis and quantification of these genes' expression. The effects of kinesin family member 23 (KIF23) were verified through functional experiments in vitro and a mouse xenograft model. The NLPR3 activator, nigericin, was applied for further analyzing the potential regulatory mechanism of KIF23 in CC. RESULTS: A total of 8 pyroptosis-related DEGs were screened out, among which 4 candidate core genes were identified as candidate hub genes and confirmed upregulation in CC tissues and cells. These genes respectively showed a positive correlation with the infiltration of distinct immune cells or tumor purity. Downregulation of KIF23 could suppress the proliferation, migration, and invasion abilities in CC cells and tumorigenesis through enhancing pyroptosis. Conversely, KIF23 overexpression accelerated the malignant phenotypes of CC cells and inhibited pyroptosis activation, which was blocked by nigericin treatment. CONCLUSIONS: KIF23 may play an oncogenic role in CC progression via inhibition of the NLRP3-mediated pyroptosis pathway.

A case report of atypical chronic myeloid leukemia with complete hematological and major molecular response to Venetoclax/Azacitidine treatment.

Atypical Chronic Myeloid Leukemia (aCML), a myeloproliferative neoplasm with poor prognosis, was reclassified as aCML by the ICC classification, and as MDS/MPN with neutrophilia by the WHO 2022 classification. Due to the heterogeneity of its clinical features and the lack of unique biomarkers, as well as limited treatment options, aCML currently lacks a standardized treatment protocol. In this case report, we reviewed a young man diagnosed with aCML who achieved complete clinical and hematologic remission subsequent to receiving a therapeutic regimen combining Venetoclax and Azacitidine.

Delineating molecular regulatory network of meat quality of longissimus dorsi indicated by transcriptomic, proteomic, and metabolomics analysis in rabbit.

This study aims to investigate the potential regulatory network responsible for the meat quality using multi-omics to help developing better varieties. Slaughter performance and meat quality of Shuxing No.1 rabbit outperformed IRA rabbit according to the tested rabbit parameters. Differentially expressed genes (DEGs) and differentially abundance proteins (DAPs) were involved in meat quality-related pathways, such as PI3K - Akt and MAPK signaling pathways. Only SMTNL1 and PM20D2 shared between DEGs and DAPs. Olfactory-sensitive undecanal, a differentially abundant metabolite (DAM) in volatilomics (vDAMs), correlated with all of the remaining 11 vDAMs, and most of 12 vDAMs were associated with amino acid metabolism. Integration revealed that 829 DEGs/DAPs were associated with 15 DAMs in four KEGG pathways, such as melatonin (a DAM in widely targeted metabolomics) was significantly positively correlated with ALDH and negatively correlated with RAB3D and CAT in the tryptophan metabolism pathway. This study sheds light on the potential mechanisms that contribute to the improved meat quality and flavor. SIGNIFICANCE: Shuxing No.1 rabbit is a new breed of meat rabbit in the Chinese market. In meat marketing, meat quality usually determines the purchase intention of consumers. Determining the biological and molecular mechanisms of meat quality in meat rabbit is essential for developing strategies to improve meat quality. According to the tested rabbit parameters, this study ascertained that the slaughter performance and meat quality of Shuxing No.1 rabbit surpasses that of IRA rabbit. The present study profiled the transcriptome, proteome, widely targeted metabolome, and volatilome of longissimus dorsi from Shuxing No.1 rabbit and IRA rabbit. The study found that meat quality and flavor-related tryptophan metabolism pathway is enriched with many DEGs/DAPs (including ALDH, RAB3D, and CAT), as well as a DAM, melatonin. This study sheds light on the potential mechanisms that contribute to the improved meat quality and flavor.

Establishment and application of recombinase polymerase amplification combined with a lateral flow dipstick for the detection of mcr-1 in uncultured clinical samples.

OBJECTIVES: The rapid dissemination of the mcr-1 gene via plasmid-mediated transfer has raised concerns regarding the efficacy of colistin as a last-resort treatment for multidrug-resistant Gram-negative bacterial infections. Current mcr-1 gene detection methods mainly focus on cultured bacteria, which is a complex and time-consuming process requiring skilled personnel, making it unsuitable for field analysis. METHODS: A rapid detection technique combining recombinase polymerase amplification with a lateral flow dipstick targeting uncultured clinical samples was developed. RESULTS: This new method targeting the mcr-1 gene region (23 232-23 642 bp, no. KP347127.1) achieved a low detection limit of 10 copies/µL. The whole process was carried out with high specificity and was completed within 20 min. The evaluation assay was conducted using 45 human faecal samples; 16 strains yielded a 98% accuracy, closely matching antimicrobial susceptibility outcomes. CONCLUSIONS: The novel method integrates nucleic acid extraction, isothermal amplification, and a test assay, suggesting the potential for timely colistin resistance surveillance in frontline disease control and healthcare settings, supporting future prevention and clinical standardization efforts.

Anomalous Detachment Behavior and Directional Reconstruction Regulation of Leaching-Type Precatalysts for Industrial Water Electrolyzers.

Current reconstruction chemistry studies are mainly operated at the laboratory scale, where the operating parameters are different from those used in industrial water electrolyzers. This gap leads to unclear reconstruction behaviors under industrial conditions and constrains the application of catalysts. Here, this work presents a new reconstruction mechanism and anomalous detachment phenomena observed in leaching-type oxygen-evolving precatalysts under industrial conditions, different from the reported results obtained under laboratory conditions. The identified detachment issues are closely linked to the production of a potassium salt separate phase, which proves sensitive to the local environment, and its instability easily leads to catalyst stripping from the substrate. By establishing detachment critical point and operating parameter-detachment correlation, a targeted reconstruction strategy is proposed to achieve smooth ligand leaching and effectively solve the detachment issue. Theoretical analyses validate the dual-site regulation in directionally reconstructed catalysts with optimized intermediate adsorption. Under industrial conditions, the coupled electrolyzer delivers an industrial-level current density at low cell voltage with prolonged durability, 1 A cm-2 at 2 V for over 340 h. This work bridges the gap of leaching-type precatalysts between laboratory test conditions and industrial operating conditions.

p53 suppresses the inflammatory response following respiratory syncytial virus infection by inhibiting TLR2.

-Respiratory syncytial virus (RSV) is a pivotal virus leading to acute lower respiratory tract infections in children under 5 years old. This study aimed to explore the correlation between p53 and Toll-like receptors (TLRs) post RSV infection. p53 levels exhibited a substantial decrease in nasopharyngeal aspirates (NPAs) from infants with RSV infection compared to control group. Manipulating p53 expression had no significant impact on RSV replication or interferon signaling pathway. Suppression of p53 expression led to heightened inflammation following RSV infection in A549 cells or airways of BALB/c mice. while stabilizing p53 expression using Nutlin-3a mitigated the inflammatory response in A549 cells. Additionally, Inhibiting p53 expression significantly increased Toll-like receptor 2 (TLR2) expression in RSV-infected epithelial cells and BALB/c mice. Furthermore, the TLR2 inhibitor, C29, effectively reduced inflammation mediated by p53 in A549 cells. Collectively, our results indicate that p53 modulates the inflammatory response after RSV infection through TLR2.

Coexistence of a novel SRBD1-ALK, ALK-CACNA1D double-fusion in a lung adenocarcinoma patient and response to alectinib: A case report.

A Chinese male patient with advanced lung adenocarcinoma experienced disease progression one and a half years after receiving first-line immunochemotherapy. The second biopsy was performed and tissue immunohistochemistry revealed Anaplastic lymphoma kinase (ALK) expression in the cytoplasm of tumor cells, so he began to receive Alectinib treatment. Then the next generation sequencing found double fusion variants of S1 RNA binding domain 1 (SRBD1)- ALK and ALK- Calcium voltage-gated channel subunit alpha1 D (CACNA1D). After continuous Alectinib treatment for 7 months, almost complete response (CR) was achieved. The patient is currently taking Alectinib for 13 months, the condition is stable, and is waiting for the next cycle of efficacy evaluation.

Ultrasound for monitoring different stages of post-transplant lymphoproliferative disorder in a transplanted kidney: A case report and review of the literature.

RATIONALE: Post-transplant lymphoproliferative disorder (PTLD) is a well-recognized, but uncommon complication in patients with kidney transplantation, which poses challenges in diagnosis and poor prognosis due to its low incidence and nonspecific clinical manifestations. As a routine follow-up examination method for kidney transplant patients, ultrasound (US) plays a significant role in the diagnosis of PTLD. Therefore, it is critical to evaluate the ultrasonic characteristics of PTLD in transplanted kidney patients for early detection and diagnosis. PATIENT CONCERNS: A 59-year-old female patient was unexpectedly found with a mass in the hilum of the transplanted kidney 12th month after transplantation, which gradually grew up in the following 4 months. The latest US examination found hydronephrosis. Contrast-enhanced ultrasound (CEUS) demonstrated a hypo-enhancement pattern in arterial and parenchymal phases and showed a new irregular area lacking perceivable intensification within the mass, which was considered necrosis. Meanwhile, the patient developed an acute increase in serum creatinine from 122 to 195 µmol/L. DIAGNOSIS: A US-guided biopsy was conducted with the final pathological diagnosis of PTLD (polymorphic). INTERVENTIONS: After receiving 3 times of rituximab and symptomatic treatment, blood creatinine returned to normal but the mass was still progressing in the patient. Therefore, the treatment approach was modified to immune-chemotherapy. OUTCOMES: The patient was in a stable condition to date. LESSONS: PTLD is a rare complication in a transplanted kidney. US and CEUS are the preferred imaging methods in renal transplant patients due to their good repeatability and no nephrotoxicity. This case demonstrates that continuous dynamic monitoring by using US and CEUS has significant value in the detection and diagnosis of PTLD in a transplanted kidney, suggesting early clinical intervention to avoid further progression.

Characteristics and prognosis of EGFR mutations in small cell lung cancer patients in the NGS era.

PURPOSE: Targeted therapy has not been effective for small cell lung cancer (SCLC) patients. Although some studies have reported on EGFR mutations in SCLC, a systematic investigation into the clinical, immunohistochemical, and molecular characteristics and prognosis of EGFR-mutated SCLCs is lacking. METHODS: Fifty-seven SCLC patients underwent next-generation sequencing technology, with 11 in having EGFR mutations (group A) and 46 without (group B). Immunohistochemistry markers were assessed, and the clinical features and first-line treatment outcomes of both groups were analyzed. RESULTS: Group A consisted primarily of non-smokers (63.6%), females (54.5%), and peripheral-type tumors (54.5%), while group B mainly comprised heavy smokers (71.7%), males (84.8%), and central-type tumors (67.4%). Both groups showed similar immunohistochemistry results and had RB1 and TP53 mutations. When treated with tyrosine kinase inhibitors (TKIs) plus chemotherapy, group A had a higher treatment response rate with overall response and disease control rates of 80% and 100%, respectively, compared to 57.1% and 100% in group B. Group A also had a significantly longer median progression-free survival (8.20 months, 95% CI 6.91-9.49 months) than group B (2.97 months, 95% CI 2.79-3.15), with a significant difference (P = 0.043). Additionally, the median overall survival was significantly longer in group A (16.70 months, 95% CI 1.20-32.21) than in group B (7.37 months, 95% CI 3.85-10.89) (P = 0.016). CONCLUSION: EGFR-mutated SCLCs occurred more frequently in non-smoking females and were linked to prolonged survival, implying a positive prognostic impact. These SCLCs shared immunohistochemical similarities with conventional SCLCs, and both types had prevalent RB1 and TP53 mutations.

Analysis of Risk Factors of Pelvic Organ Prolapse in Postmenopausal Women and Construction of Prediction Model.

Background: The incidence of Pelvic organ prolapse (POP) was as high as 50% in women, with the main symptoms of vaginal tissue prolapse, accompanied by urination, defecation, and sexual dysfunction, which affected patients' quality of life. POP is more prominent in postmenopausal women due to various factors. By constructing a model, we predict POP and expect to reduce the incidence of POP. Objective: To explore the risk factors for POP in postmenopausal women and develop a predictive model that can identify high-risk individuals early so that targeted preventive measures can be taken to reduce the burden of POP. Methods: Using retrospective studies, 290 menopausal women treated in the Department of Gynecology of the Ninth People's Hospital of Suzhou from January 2019 to December 2022 were selected as the study subjects. Women with menopause were divided into the POP group (62 cases) and a non-POP group (228 cases) according to whether or not POP occurred. Single factor analysis was performed on the two data groups. The risk factors of POP in menopausal women were screened by multivariate logistic regression analysis. Based on the screening results, a graph prediction model expressed as a nomogram is constructed. The model's effectiveness was analyzed by the goodness of fit test and receiver operating characteristic curve (ROC) curve. The decision curve was used to analyze the clinical effectiveness of the model. Results: Multifactor logistic regression analysis showed that Older age (OR = 2.309, P = .007), more childbirth frequency (OR = 3.121, P = .002), low expression of estradiol (E2) (OR = 1.499, P = .023), low expression of serum 25-hydroxyvitamin D3[25-(OH)D3] (OR = 2.073, P = .011), and lower blood calcium (OR = 21.677, P = .014) were all risk factors for POP in menopausal women. Based on the above indicators, a risk prediction model is constructed. The model has been proved to have good recognition ability, areas under curve (AUC) = 0.887 (95%CI: 0.845-0.926), The best cutoff value is 0.37, The sensitivity and specificity were 0.885 and 0.840, respectively; The goodness of fit test showed that the predicted value of the model had no statistical significance with the actual value. The threshold probability is in the range of 1%~99%. The net benefit of menopausal women is higher than the other two extreme curves. It shows that the model is clinically effective. Conclusion: Age, times of delivery, E2, 25-(OH)D3, and blood calcium are related to POP in menopausal women. A nomogram model based on these 5 indicators can effectively assess the risk of POP in postmenopausal women. The clinician can use this column chart to calculate the risk of POP occurrence for each patient and make clinical recommendations accordingly.

Clinical value of ultrasound in adult Wilms' tumor patient with uremia: A case report and literature review.

RATIONALE: Wilms' tumor (WT) is the most common pediatric kidney malignancy and is rarely found in adults. Nonspecific clinical symptoms and imaging features often lead to delayed diagnosis or misdiagnosis of adult WT, resulting in poor clinical outcomes. Ultrasound (US), as an efficient and noninvasive examination method, has been widely used in clinical diagnosis and treatment. Therefore, various US evidence is meaningful to improve understanding of adult WT characteristics in ultrasound. PATIENT CONCERNS: A 45-year-old female patient with uremia (regular hemodialysis for 13 years) with painless gross hematuria was diagnosed with a right kidney tumor penetrating to the lung. Preoperatively, B-mode ultrasonography showed an ill-defined hyperechoic mass in the right kidney, which revealed an unclear border, uneven internal echoes, and calcification. Besides, the internal blood flow signal of the tumor was detected. Contrast-enhanced ultrasound (CEUS) showed an uneven hyper-enhancement in the tumor ("fast in and slow out"). Contrast-enhanced computed tomography of the kidney indicated a similar result as the CEUS. Moreover, the chest CT identified multiple pulmonary metastatic nodules. DIAGNOSES: An ultrasound-guided percutaneous core needle biopsy of the tumor proceeded to make a definite diagnosis of adult WT (epithelial type). INTERVENTIONS: The patient was treated with tislelizumab. OUTCOMES: No progress was found to date. LESSONS: We report the first case in which CEUS was performed in an adult WT patient with uremia and multiple pulmonary metastases. The features obtained by the US can help in the diagnosis of adult WT and direct further diagnostic procedures.

Andrographolide Attenuates RSV-induced Inflammation by Suppressing Apoptosis and Promoting Pyroptosis after Respiratory Syncytial Virus Infection In Vitro.

BACKGROUND: Respiratory syncytial virus (RSV), which is the predominant viral pathogen responsible for causing acute lower respiratory tract infections in children, currently lacks specific therapeutic drugs. Despite andrographolide's demonstrated effectiveness against various viral infections, its effects on RSV infection remain unclear. METHODS: In this study, RSV infection and andrographolide-intervened A549 cell lines were used. The virus load of RSV and the levels of IL-6 and IL-8 in the cell supernatant were quantified. The potential targets of andrographolide in the treatment of RSV-infected airway epithelial cells were analyzed using the Gene Expression Omnibus (GEO) database and the PharmMapper Database, and the changes in mRNA expression of these target genes were measured. To further illustrate the effect of andrographolide on the death pattern of RSV-infected airway epithelial cells, Annexin V-FITC/PI apoptosis assays and Western blotting were conducted. RESULTS: Andrographolide decreased the viral load and attenuated IL-6 and IL-8 levels in cell supernatant post-RSV infection. A total of 25 potential targets of andrographolide in the treatment of RSV-infected airway epithelial cells were discovered, and CASP1, CCL5, JAK2, and STAT1 were identified as significant players. Andrographolide noticeably suppressed the increased mRNA expressions of these genes post-RSV infection as well as IL-1ß. The flow cytometry analysis demonstrated that andrographolide alleviated apoptosis in RSV-infected cells. Additionally, RSV infection decreased the protein levels of caspase-1, cleaved caspase-1, cleaved IL-1ß, N-terminal of GSDMD, and Bcl-2. Conversely, andrographolide increased their levels. CONCLUSION: These results suggest that andrographolide may reduce RSV-induced inflammation by suppressing apoptosis and promoting pyroptosis in epithelial cells, leading to effective viral clearance.

Combined small cell lung cancer: current progress and unmet needs.

Combined small cell lung cancer (CSCLC) is a specific subtype of lung cancer characterized by a pathological mixture of small cell lung cancer and any subtype of non-small cell lung cancer components. Currently, our understanding of the clinicopathological features, origin, molecular characterization, treatment, and prognosis of CSCLC remains limited. CSCLCs represent examples of intratumor heterogeneity and pose challenges for accurate diagnosis. Are there any distinct clinicopathologic and molecular differences between pure SCLC and CSCLC? Furthermore, the prognostic outcomes and optimal treatments for CSCLC are urgently needed. This article aims to summarize the current biological features and clinical management of CSCLC, providing a reference for further understanding of this heterogeneous form of small cell lung cancer.

Recurrent pleural effusion as a rare manifestation after prolonged PD1 inhibitor (camrelizumab)-based immunotherapy: A case report.

Immune-related adverse events (irAEs) pose a significant challenge for the widespread adoption of immuno-oncology therapies, but their symptoms can vary widely. In particular, the relationship between irAEs and pleural effusion (PE) in patients with advanced non-small cell lung cancer (NSCLC) remains unclear. In this report, we present the case of an advanced NSCLC patient who developed persistent PE despite receiving camrelizumab (an anti-programmed death receptor 1 [PD-1] antibody) and chemotherapy as first-line treatment. While the patient's tumor biomarkers decreased after multiple cycles of treatment, the PE persisted despite negative findings on cytology and pleural biopsy. Additionally, the use of anti-angiogenic drugs failed to alleviate the PE. Screening for rheumatic connective tissue markers and tuberculosis yielded negative results, but intrathoracic dexamethasone injections in two doses resulted in a significant reduction of the PE. This case suggests that PE may represent a rare type of irAE that should be monitored for during prolonged immuno-oncology therapy.

Effects of combining immune checkpoint inhibitors and anti-angiogenic agents on bone metastasis in non-small cell lung cancer patients.

This study aimed to evaluate the efficacy of combining immune checkpoint inhibitors (ICIs) and anti-angiogenic agents in treating lung cancer patients with bone metastases (BMs), as it is unclear whether this combination is effective for this condition. Non-small cell lung cancer patients with BMs receiving ICIs were divided into experimental and control groups based on anti-angiogenic treatment. Progression-free survival (PFS) and overall survival (OS) were evaluated using the Kaplan-Meier method, with log-rank test for comparisons. Prognostic factors were determined by univariate and multivariate Cox regression analyses. The study included 95 patients. The experimental group (n = 42) had a higher disease control rate (DCR) (90.5% vs. 68.6%, p = .009), objective response rate (ORR) (35.7% vs. 24.5%, p = .235), and longer median bone PFS (14.3 months vs. 8.3 months, p = .011) for bone metastasis. However, there were no significant differences in overall DCR (92.8% vs. 86.7%, p = .339), ORR (64.3% vs. 62.3%, p = .839), and PFS (12.4 months vs. 11.6 months, p = 0.383) between the 2 groups. The experimental group had a lower incidence of skeleton-related events (SREs) (28.6% vs. 35.8%, p = .425), and SRE patients had shorter PFS (7.7 vs. 14.3 months, p < .001) and OS (12.1 vs. 19.0 months, p = .028). Anti-angiogenic therapy (HR = 0.55, p = .012) and SRE (HR = 2.93, p < .001) were identified as independent prognostic factors for bone metastatic PFS. Adverse events were slightly higher in the experimental group (29.3% vs. 18.9%, p = .238), but not statistically significant. The combination of ICIs and anti-angiogenic agents leads to a significant PFS for BMs and potentially decreases SRE.