Efficacy and safety of sintilimab in combination with chemotherapy for recurrent extensive-stage small cell lung cancer: a real-world retrospective study.

Background: Immune checkpoint inhibitors (ICIs) no longer are approved for second-line or later treatment of extensive-stage small cell lung cancer (ES-SCLC), and have not been studied in combination with chemotherapy. Exploring the efficacy and safety of second-line or later immunotherapy for ES-SCLC is an urgent clinical question that needs to be addressed, and combination therapies are an important research direction. This study intended to investigate the efficacy and safety of the sintilimab in combination with chemotherapy as a second-line and beyond treatment option for ES-SCLC. Methods: Medical records of patients who received treatment with sintilimab in combination with chemotherapy or chemotherapy alone as a second-line or beyond therapy were retrospectively analyzed. The study evaluated efficacy and safety. Indicators of efficacy included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Safety indicators included adverse events (AEs). Results: This cohort comprised of 46 patients: 24 in the sintilimab combination chemotherapy group and 22 in the chemotherapy group. Chemotherapy received by both groups was either albumin-bound paclitaxel or irinotecan. Compared with the chemotherapy group, the sintilimab combination chemotherapy group had higher ORR and DCR (ORR: 37.5% vs. 9.1%, P=0.04; DCR: 75.0% vs. 40.9%, P=0.04), and significantly prolonged PFS and OS [median PFS (mPFS): 5.07 vs. 2.45 months, P=0.006; median OS (mOS): 14.43 vs. 10.34 months, P=0.009]. Also, there was no significant increase in the incidence of AEs in the sintilimab combination chemotherapy group, which was well tolerated by patients. Conclusions: Sintilimab in combination with chemotherapy is superior to single-agent chemotherapeutic treatment as second-line or later therapy in ES-SCLC patients who have not received prior immunotherapy. These results need to be confirmed in future clinical trials.

Specific feature recognition on group specific networks (SFR-GSN): a biomarker identification model for cancer stages.

Background and Objective: Accurate identification of cancer stages is challenging due to the complexity and heterogeneity of the disease. Current clinical diagnosis methods primarily rely on phenotypic observations, which may not capture early molecular-level changes accurately. Methods: In this study, a novel biomarker recognition method was proposed tailored for cancer stages by considering the change of gene expression relationships. Utilizing the sample-specific information and protein-protein interaction networks, the group specific networks were constructed to address the limited specificity of potential biomarkers. Then, a specific feature recognition method was proposed based on these group specific networks, which employed the random forest algorithm for initial screening followed by a recursive feature elimination process to identify the optimal biomarker subset. During exploring optimal results, a strategy termed the Cost-Benefit Ratio, was devised to facilitate the identification of stage-specific biomarkers. Results: Comparative experiments were conducted on lung adenocarcinoma and breast cancer datasets to validate the method's efficacy and generalizability. The results showed that the identified biomarkers were highly stage-specific, and the F1 scores for predicting cancer stages were significantly improved. For the lung adenocarcinoma dataset, the F1 score reached 97.68%, and for the breast cancer dataset, it achieved 96.87%. These results significantly surpassed those of three conventional methods in terms of F1 scores. Moreover, from the perspective of biological functions, the biomarkers were proved playing an important role in cancer stage-evolution. Conclusion: The proposed method demonstrated its effectiveness in identifying stage-related biomarkers. By using these biomarkers as features, accurate prediction of cancer stages was achieved. Furthermore, the method exhibited potential for biomarker identification in subtype analyses, offering novel perspectives for cancer prognosis.

Massive Hepatocellular Carcinoma Combined With Giant Uterine Fibroid on 18F-FDG PET/CT.

ABSTRACT: A 50-year-old woman was admitted due to a liver mass discovered by ultrasound in routine physical examination. MRI demonstrated a large hepatocellular carcinoma. It also discovered an abdominal mass simultaneously. 18F-FDG PET/CT was performed for staging. PET/CT showed mixed and mild metabolism of the hepatic lesion and giant abdominopelvic mass, respectively. Hepatocellular carcinoma combined with a benign mass in abdominopelvic cavity from uterine was considered and finally proved pathologically. We present a rare case of woman with large liver cancer accompanied by giant uterine fibroid where 18F-FDG PET/CT helped in making the right diagnosis.

Hypocretenolides: collective total syntheses and activities toward metastatic colon cancer.

A concise and collective synthetic route to hypocretenolides was developed for the first time. This route features one-pot addition-alkylation and intramolecular 1,3-dipolar cycloaddition to efficiently assemble the 5/7/6 ring system. Our syntheses enabled multigram preparation of hypocretenolide which facilitated further biological evaluation. Preliminary CCK-8 cytotoxic results of hypocretenolide indicated its IC50 values within 1 µM against 4 colon cancer cell lines. Wound healing and transwell assays suggested the promising inhibitory activities of hypocretenolide toward the migratory capabilities of colon cancer cells in vitro. The animal results confirmed that hypocretenolide can inhibit metastasis of colon cancer cells.

Long-term survival of a patient with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) and untreated multiple brain metastases treated with zorifertinib: A case report.

Brain metastases (BM) are common in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) and confer poor prognoses. Zorifertinib (AZD3759), an EGFR-tyrosine kinase inhibitor (TKI) with high blood-brain barrier penetration, has previously demonstrated promising systemic and intracranial antitumor activity in phase 1-3 studies. This is the first report of a patient with EGFR-mutant (exon 21 L858R) NSCLC and symptomatic untreated multiple BM who achieved a long overall survival (OS) of more than 65 months after sequential treatment with zorifertinib and a third-generation EGFR-TKI. This new treatment paradigm offers a new treatment option and deserves further clinical exploration to prolong OS of patients with EGFR-mutant NSCLC and untreated multiple BM.

Universal crRNA Acylation Strategy for Robust Photo-Initiated One-Pot CRISPR-Cas12a Nucleic Acid Diagnostics.

Spatiotemporal regulation of clustered regularly interspaced short palindromic repeats (CRISPR) system is attractive for precise gene editing and accurate molecular diagnosis. Although many efforts have been made, versatile and efficient strategies to control CRISPR system are still desirable. Here, we proposed a universal and accessible acylation strategy to regulate the CRISPR-Cas12a system by efficient acylation of 2'-hydroxyls (2'-OH) on crRNA strand with photolabile agents (PLGs). The introduction of PLGs confers efficient suppression of crRNA function and rapid restoration of CRISPR-Cas12a reaction upon short light exposure regardless of crRNA sequences. Based on this strategy, we constructed a universal PhotO-Initiated CRISPR-Cas12a system for Robust One-pot Testing (POIROT) platform integrated with recombinase polymerase amplification (RPA), which showed two orders of magnitude more sensitive than the conventional one-step assay and comparable to the two-step assay. For clinical sample testing, POIROT achieved high-efficiency detection performance comparable to the gold-standard quantitative PCR (qPCR) in sensitivity and specificity, but faster than the qPCR method. Overall, we believe the proposed strategy will promote the development of many other universal photo-controlled CRISPR technologies for one-pot assay, and even expand applications in the fields of controllable CRISPR-based genomic editing, disease therapy, and cell imaging.

WNT-inhibitory factor 1-mediated glycolysis protects photoreceptor cells in diabetic retinopathy.

BACKGROUND: In diabetic retinopathy (DR), hypoxia-inducible factor (HIF-1α) induces oxidative stress by upregulating glycolysis. This process leads to neurodegeneration, particularly photoreceptor cell damage, which further contributes to retinal microvascular deterioration. Further, the regulation of Wnt-inhibitory factor 1 (WIF1), a secreted Wnt signaling antagonist, has not been fully characterized in neurodegenerative eye diseases. We aimed to explore the impact of WIF1 on photoreceptor function within the context of DR. METHOD: Twelve-week-old C57BL/KsJ-db/db mice were intravitreally injected with WIF1 overexpression lentivirus. After 4 weeks, optical coherence tomography (OCT), transmission electron microscopy (TEM), H&E staining, and electroretinography (ERG) were used to assess the retinal tissue and function. The potential mechanism of action of WIF1 in photoreceptor cells was explored using single-cell RNA sequencing. Under high-glucose conditions, 661 W cells were used as an in vitro DR model. WIF1-mediated signaling pathway components were assessed using quantitative real-time PCR, immunostaining, and western blotting. RESULT: Typical diabetic manifestations were observed in db/db mice. Notably, the expression of WIF1 was decreased at the mRNA and protein levels. These pathological manifestations and visual function improved after WIF1 overexpression in db/db mice. TEM demonstrated that WIF1 restored damaged mitochondria, the Golgi apparatus, and photoreceptor outer segments. Moreover, ERG indicated the recovery of a-wave potential amplitude. Single-cell RNA sequencing and in vitro experiments suggested that WIF1 overexpression prevented the expression of glycolytic enzymes and lactate production by inhibiting the canonical Wnt signaling pathway, HIF-1α, and Glut1, thereby reducing retinal and cellular reactive oxygen species levels and maintaining 661 W cell viability. CONCLUSIONS: WIF1 exerts an inhibitory effect on the Wnt/ß-catenin-HIF-1α-Glut1 glycolytic pathway, thereby alleviating oxidative stress levels and mitigating pathological structural characteristics in retinal photoreceptor cells. This mechanism helps preserve the function of photoreceptor cells in DR and indicates that WIF1 holds promise as a potential therapeutic candidate for DR and other neurodegenerative ocular disorders.

Anlotinib plus docetaxel vs. docetaxel alone for advanced non-small-cell lung cancer patients who failed first-line treatment: A multicenter, randomized phase II trial.

OBJECTIVES: Given the modest efficacy of docetaxel in advanced non-small cell lung cancer (NSCLC), this study assesses the therapeutic potential and safety profile of anlotinib in combination with docetaxel compared to docetaxel monotherapy as a second-line therapy for patients with advanced NSCLC. MATERIALS AND METHODS: In this phase II study, patients with advanced NSCLC experiencing failure with first-line platinum-based regimens were randomized in a 1:1 ratio to receive either anlotinib plus docetaxel or docetaxel alone. Primary endpoint was progression-free survival (PFS), with overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety as secondary endpoints. RESULTS: A total of 83 patients were randomized. The combination of anlotinib and docetaxel significantly extended median PFS to 4.4 months compared to 1.6 months for docetaxel alone (hazard ratio [HR] = 0.38, 95 % confidence interval [CI]: 0.23-0.63, P = 0.0002), and also demonstrated superior ORR (32.5 % vs. 9.3 %, P = 0.0089) and DCR (87.5 % vs. 53.5 %, P = 0.0007). Median OS was observed at 12.0 months in the combination group vs. 10.9 months in the monotherapy group (HR = 0.82, 95 % CI: 0.47-1.43, P = 0.4803). For patients previously treated with immunotherapy, the median PFS was notably longer at 7.8 vs. 1.7 months (HR = 0.22, 95 % CI: 0.09-0.51, P = 0.0290). The incidence of grade ≥ 3 treatment-related adverse events, predominantly leukopenia (15.0 % vs. 7.0 %) and neutropenia (10.0 % vs. 5.0 %), was manageable across both groups. CONCLUSION: Anlotinib plus docetaxel offers a viable therapeutic alternative for patients with advanced NSCLC who failed first-line platinum-based treatments.

Deciphering the molecular and clinical characteristics of TREM2, HCST, and TYROBP in cancer immunity: A comprehensive pan-cancer study.

Background: Hematopoietic cell signal transducer (HCST) and tyrosine kinase-binding protein (TYROBP) are triggering receptors expressed on myeloid cells 2 (TREM2), which are pivotal in the immune response to disease. Despite growing evidence underscoring the significance of TREM2, HCST, and TYROBP in certain forms of tumorigenesis, a comprehensive pan-cancer analysis of these proteins is lacking. Methods: Multiple databases were synthesized to investigate the relationship between TREM2, HCST, TYROBP, and various cancer types. These include prognosis, methylation, regulation by long non-coding RNAs and transcription factors, immune signatures, pathway activity, microsatellite instability (MSI), tumor mutational burden (TMB), single-cell transcriptome profiling, and drug sensitivity. Results: TREM2, HCST, and TYROBP displayed extensive somatic changes across numerous tumors, and their mRNA expression and methylation levels influenced patient outcomes across multiple cancer types. long non-coding RNA (lncRNA) -messenger RNA (mRNA) and TF-mRNA regulatory networks involving TREM2, HCST, and TYROBP were identified, with lncRNA MEG3 and the transcription factor SIP1 emerging as potential key regulators. Further immune analyses indicated that TREM2, HCST, and TYROBP play critical roles in immune-related pathways and macrophage differentiation, and may be significantly associated with TGF-ß and SMAD9. Furthermore, the expression of TREM2, HCST, and TYROBP correlated with the immunotherapy markers TMB and MSI, and influenced sensitivity to immune-targeted drugs, thereby indicating their potential as predictors of immunotherapy outcomes. Conclusion: This study offers valuable insights into the roles of TREM2, HCST, and TYROBP in tumor immunotherapy, suggesting their potential as prognostic markers and therapeutic targets for various cancers.

Camrelizumab combined with apatinib and nanoparticle albumin-bound paclitaxel in lung adenocarcinoma (CAPAP-lung): a single-arm phase II study.

Background: Platinum-doublet chemotherapy plus immunotherapy has been the standard of care for the first-line treatment of advanced non-small cell lung cancer lacking actional driver mutations. However, optimization of drug combinations is still needed to find a better balance between therapeutic efficacy and safety in the immunotherapy era. We aimed to investigate the efficacy and safety of platinum-free albumin bound paclitaxel (nab-paclitaxel) combined with camrelizumab and apatinib as first-line treatment for patients with advanced lung adenocarcinoma. Methods: In this multicenter open-label, single-arm phase II trial, patients with systemic treatment-naïve advanced lung adenocarcinoma without epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) mutations received a rational-based combination of camrelizumab (200 mg intravenously, day one), apatinib (250 mg, q.d., five continuous days per week), and nab-paclitaxel (135 mg/m2 intravenously, days one and eight) every three weeks for four to six cycles in China. Patients with controlled disease were maintained with camrelizumab and apatinib. The primary end point was progression-free survival (PFS). This trial is registered with ClinicalTrials.gov (No. NCT04459078). Findings: Between August 26, 2020 and May 20, 2022, 64 patients were enrolled. The median PFS was 14.3 (95% CI: 9.9, not reached) months. The confirmed objective response rate was 64.1% (95% CI: 51.1, 75.7). The grade 3-4 hematologic treatment-related adverse events (TRAEs) were decreased neutrophil count (14.1%), decreased white blood cell count (7.8%), and anemia (3.1%). The most common non-hematologic TRAEs of grade 3-4 were increased alanine transaminase (18.8%) and aspartate transaminase (15.6%). No treatment-related death occurred. The quality of life was on average not clinically meaningful worse through treatment cycle 14. Interpretation: Nab-paclitaxel plus camrelizumab and apatinib showed clinically meaningful anti-tumor activity and manageable safety, with few hematologic toxicities, and might be a potential treatment option in patients with advanced lung adenocarcinoma lacking EGFR/ALK mutations. Funding: Heath Research Foundation of Chinese Society of Clinical Oncology, Hunan Provincial Natural Science Foundation of China, Hunan Cancer Hospital Climb Plan, Sister Institution Network Fund of The University of Texas MD Anderson Cancer Center, The Science and Technology Innovation Program of Hunan Province, and Suzhou Sheng Diya Biomedical Co., Ltd, a subsidiary of Jiangsu Hengrui Pharmaceuticals Co., Ltd. (Shanghai, China).

A phase Ib/II study of cadonilimab (PD-1/CTLA-4 bispecific antibody) plus anlotinib as first-line treatment in patients with advanced non-small cell lung cancer.

BACKGROUND: Cadonilimab is a bispecific antibody that simultaneously targets programmed cell death receptor-1 and cytotoxic T lymphocyte-associated antigen-4. This study aimed to assess the safety and efficacy of cadonilimab plus anlotinib for the first-line treatment of advanced non-small cell lung cancer (NSCLC) without sensitizing EGFR/ALK/ROS1 mutations. METHODS: Patients received cadonilimab 15 mg/kg and 10 mg/kg every three weeks (Q3W) plus anlotinib at doses of 10 or 12 mg once daily for two weeks on a one-week-off schedule. The primary endpoints included safety and objective response rate (ORR). RESULTS: Sixty-nine treatment-naïve patients received cadonilimab 15 mg/kg Q3W combination (n = 49) and 10 mg/kg Q3W combination (n = 20). Treatment-related adverse events (TRAEs) were reported in 48 (98.0%) and 19 (95.0%) patients, with grade ≥3 TRAEs occurring in 29 (59.2%) and five (25.0%) patients, respectively. TRAEs leading to cadonilimab discontinuation occurred in eight (16.3%) and one (5.0%) patients in the cadonilimab 15 mg/kg Q3W and 10 mg/kg Q3W dosing groups. The confirmed ORRs were 51.0% (25/49) and 60.0% (12/20) accordingly. CONCLUSIONS: Cadonilimab 10 mg/kg Q3W plus anlotinib showed manageable safety and promising efficacy as a first-line chemo-free treatment for advanced NSCLC. GOV IDENTIFIER: NCT04646330.

Virgin Camellia Seed Oil Improves Glycolipid Metabolism in the Kidney of High Fat-Fed Rats through AMPK-SREBP Pathway.

Camellia seed oil (CO) is used as edible oil in southern China because of its excellent fatty acid composition and abundant bioactive compounds. Chronic kidney disease (CKD) is one of the most common chronic degenerative diseases in China, and active compounds in vegetable oil, like virgin olive oil, have been demonstrated to be efficacious in the management of CKD. In this study, virgin CO was refined using a standard process. The refining had minimal impact on the fatty acid composition, but significantly reduced the presence of bioactive compounds like polyphenols in CO. Sprague-Dawley (SD) rats fed with high fat diet (Group G) were treated with either virgin (Group Z) or refined CO (Group R). The oral administration of CO alleviated lipid accumulation and decreased body and kidney weight gain. Furthermore, treatment with virgin CO increased the renal ATP content. The renal expression levels of AMPK and key enzymes involved in fatty acid oxidation (CPT-1 and ACOX1) and glycolysis (HK, PFK, PK and GAPDH) were up-regulated in Group Z, thereby enhancing the ATP production. Virgin CO treatment downregulated the expression level of SREBP2 and its downstream target genes, such as ACC, FAS, and HMGCR, which reduced lipid synthesis. These findings indicate that virgin CO improves glycolipid metabolism and restores energy homeostasis in the kidneys of rats fed with a high-fat diet by modulating the AMPK-SREBP-signaling pathway, suggesting the potential of active compounds in virgin CO for managing the renal failure associated with glycolipid dysmetabolism.

Total Syntheses of Brassicicenes A, R, and T.

Here, we report concise and divergent total syntheses of fusicoccane members brassicicenes A, R, and T. The key feature of the synthesis is the rapid construction of the 5/8/5 tricyclic core via four steps: aldol reaction, Stork-Danheiser transposition, and ring-closing metathesis from known compounds followed by concise oxidation state adjustment.

IGF2BP1 enhances the stability of SIK2 mRNA through m6A modification to promote non-small cell lung cancer progression.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a significant public health concern globally. Evidence suggests that Salt-inducible kinase 2 (SIK2) is differentially expressed across various cancers and is also implicated in cancer progression. Despite this, the precise function of SIK2 in NSCLC is yet to be elucidated and requires further investigation. METHODS: SIK2 expression was evaluated in both HBEC and NSCLC cells, utilizing quantitative real-time PCR (qRT-PCR) and Western blot (WB) analyses. Furthermore, to identify the influence of SIK2 on cell proliferation, migration, invasion, and apoptosis, a range of techniques were employed. To evaluate N6-methyladenosine (m6A) modification levels of total RNA and SIK2 within cells, RNA m6A colorimetry and methylated RNA immunoprecipitation (MeRIP) techniques were employed. Additionally, to confirm the interaction between SIK2 and insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), bioinformatics analysis was executed, and the results were validated through RIP. The stability of SIK2 mRNA was determined using actinomycin D experiment. Furthermore, to validate the in vivo functionality of SIK2, a subcutaneous transplantation tumor model was established in nude mice. RESULTS: In this study, upregulation of SIK2 in NSCLC cells was observed. Overexpression of SIK2 was found to lead to promotion of cell proliferation, migration, invasion, and suppression of the Hippo/yes-associated protein (YAP) pathway, while inhibiting apoptosis. RIP analysis showed that IGF2BP1 protein interacted with SIK2 mRNA. Knockdown of IGF2BP1 decreased mRNA stability and m6A modification levels of SIK2. Additionally, knockdown of IGF2BP1 resulted in inhibition of cell proliferation, migration, invasion, suppression of the Hippo/YAP pathway, and promoting apoptosis. Overexpression of SIK2 overturned the impact of IGF2BP1 on NSCLC cells, which was then confirmed through in vivo experiments. CONCLUSION: IGF2BP1 stabilized SIK2 mRNA through m6A modification to promote NSCLC progression, potentially offering new diagnostic and therapeutic insights for NSCLC.

IL-18 serves as a main effector of CAF-derived METTL3 against immunosuppression of NSCLC via driving NF-κB pathway.

Background: N6-methyladenosine (m6A) is the most abundant modification in eukaryotic mRNA. However, its role in non-small cell lung cancer (NSCLC) has not been completely elucidated.Objective: To explore whether methyltransferase like 3 (METTL3) in cancer associated fibroblasts (CAFs) affects the secretion of IL-18, which drives NSCLC cells to regulate PD-L1-mediated immunosuppression via the nuclear factor kappa B (NF-κB) pathway.Methods: Histopathological features of NSCLC tissues were identified by H&E and IHC staining. The levels of m6A writers (METTL3), IL-18 and NF-κB pathway related genes were assessed. The quantity of CD8+ T cells was evaluated by flow cytometry (FCM). The direct binding relationship between METTL3 and IL-18 mRNA was detected by RIP assay and RNA pulldown and confirmed by dual - luciferase reporter assay. The level of RNA m6A was detected by RNA m6A dot blot and meRIP assays. A heterotopic implantation model of NSCLC was established in NOD-SCID mice for further explore the effect of CAF derived METTL3 on immunosuppression of NSCLC in vivo.Results: Our results illustrated that METTL3 was down-regulated in CAFs, and CAF derived METTL3 alleviated PD-L1-mediated immunosuppression of NSCLC through IL-18. Subsequently, we found that IL-18 was main effector of CAF-derived METTL3 against immunosuppression of NSCLC, and IL-18 accelerated immunosuppression of NSCLC by driving NF-κB pathway. In vivo, METTL3 knockdown-derived CAFs accelerated immunosuppression of NSCLC.Conclusion: IL-18 served as a main effector of CAF-derived METTL3 against immunosuppression of NSCLC via driving NF-κB pathway.

Efficacy and safety of dacomitinib in treatment-naïve patients with advanced NSCLC harboring uncommon EGFR mutation: an ambispective cohort study.

BACKGROUND: About 10% of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations are harbored as uncommon mutations. This study aimed to explore the efficacy and safety of dacomitinib, a second-generation EGFR tyrosine kinase inhibitor (EGFR-TKIs), in treating uncommon EGFR-mutated advanced NSCLC. METHODS: Treatment-naïve advanced NSCLC patients treated with dacomitinib at Hunan Cancer Hospital with uncommon EGFR mutations were evaluated. The primary endpoint was progression-free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety. RESULT: Between December 2019 and December 2021, a total of 16 patients was included. Median PFS was 14.0 (95% CI 4.32-23.7) months, and median OS was not reached. ORR was 68.8% (95% CI 41.3 to 89.0%) and DCR was 93.8% (95%CI 69.8 to 99.8%), including three achieving complete remission (CR) and eight achieving partial remission (PR). Median PFS for patients with brain metastasis was 9.0 (95%CI 6.9 to 11.1) months. Intracranial ORR was 100%, including 2 CR and 4 PR. Major treatment-related adverse events (TRAEs) included rash (87.5%), paronychia (62.5%), oral ulcers (50.0%), and diarrhea (50.0%), none of which were ≥ grade 3 TRAEs. CONCLUSIONS: Dacomitinib showed good activity and manageable toxicity in NSCLC patients with uncommon EGFR mutations.

Influence factors of the survival in colorectal cancer patients with second primary malignancy after surgery: A SEER database analysis.

The survival rate is significantly reduced in patients with colorectal cancer (CRC) who developing a second primary malignancy (SPM), and however, little has known about the factors that contribute to the mortality of SPMs among CRC survivors. This study aims to explore the influence factors in both the all-cause and cancer-specific mortality of patients with SPMs after CRC surgery. Data of adult CRC patients with SPMs were extracted from the Surveillance, Epidemiology, and End Results (SEER) database in this retrospective cohort study. The associations between potential influence factors and all-cause mortality and cancer-specific mortality were explored using univariate and multivariate Cox proportional hazards analyses. The evaluation indexes were hazard ratios (HRs), and 95% confidence intervals (CIs). We also drew pie charts to respectively reflect the distributions of SPMs sites and time interval in study population. A total of 1202 (56.14%) patients died for all-cause, and 464 (21.67%) died due to CRC. The results showed that after adjusting for covariates, age, sex, marital status, T stage of CRC, second primary cancer site, stage of SPMs, grade of SPMs, TNM stage of SPMs, and time interval were associated with all-cause mortality, while marital status, stage of CRC, T stage of CRC, chemotherapy, second primary cancer site, stage of SPMs, grade of SPMs, TNM stage of SPMs, and time interval were associated with cancer-specific mortality in patients with CRC. In addition, colon (23.5%) was the most common site of SPMs, followed by digestive system (19.0%), and the time interval between CRC and SPMs in most patients was over 5 years (28.4%). Our findings may assist clinicians to identify high-risk patients for SPMs after CRC surgery. Also, the postoperative long-term follow-up and close attention on the key systems where the SPMs may occur are of great necessary in patients with CRC.

M2 macrophage exosomal LINC01001 promotes non-small cell lung cancer development by affecting METTL3 and glycolysis pathway.

There have been data showing that LINC01001 is highly expressed in lung cancer, but the effect of M2 macrophage exosomal LINC01001 to METTL3, glycolysis and immunity in non-small cell lung cancer (NSCLC) has not been reported. In this study, we aimed to explore the regulatory effect and mechanism of M2 macrophage exosomal LINC01001 in NSCLC. The results of our study show that the verification of macrophage exosomes, it was confirmed that exosomes regulated proliferation, glucose intake, lactate production and ATP levels of NSCLC cells. Exosomes also promoted the expression of METTL3. Bioinformatics screening showed that LINC01001 regulated METTL3. Subsequent experiments revealed exosomal LINC01001 influenced the glycolysis processes of NSCLC cells. Through RIP, it was proved that LINC01001 functioned in combination with METTL3. Bioinformatics predicted that NASP was a METTL3-targeted gene. LINC01001 could also regulate NASP methylation. Tumorigenesis in mice also indicated that LINC01001 mediated METTL3 to stimulate the development of tumors. In this study, LINC01001 was successfully verified in the exosomes-derived from M2 macrophages. It was confirmed that LINC01001 could interact with METTL3 and regulate glycolysis process in NSCLC cells. LINC01001 also inhibited T cell proliferation.

Developing an automatic warning system for anomalous chicken dispersion and movement using deep learning and machine learning.

Chicken is a major source of dietary protein worldwide. The dispersion and movement of chickens constitute vital indicators of their health and status. This is especially evident in Taiwanese native chickens (TNCs), a local variety which is high in physical activity when healthy. Conventionally, the dispersion and movement of chicken flocks are observed in patrols. However, manual patrolling is laborious and time-consuming. Moreover, frequent patrols increase the risk of carrying pathogens into chicken farms. To address these issues, this study proposes an approach to develop an automatic warning system for anomalous dispersion and movement of chicken flocks in commercial chicken farms. Embendded systems were developed to acquire videos of chickens from overhead view in a chicken house, in which approximately 20,000 TNCs were raised for a period of 10 wk. Each video was 5-min in length. The videos were transmitted to a remote cloud server and were converted into images. A You Only Look Once-version 7 tiny (YOLOv7-tiny) object detection model was trained to detect chickens in the images. The dispersion of the chicken flocks in a 5-min long video was calculated using nearest neighbor index (NNI). The movement of the chicken flocks in a 5-min long video was quantified using simple online and real-time tracking algorithm (SORT). The normal ranges (i.e., 95% confidence intervals) of chicken dispersion and movement were established using an autoregressive integrated moving average (ARIMA) model and a seasonal autoregressive integrated moving average with exogenous factors (SARIMAX) model, respectively. The system allows farmers to check up on the chicken farm only when the dispersion or movement values were not in the normal ranges. Thus, labor time can be saved and the risk of carrying pathogens into chicken farms can be reduced. The trained YOLOv7-tiny model achieved an average precision of 98.2% in chicken detection. SORT achieved a multiple object tracking accuracy of 95.3%. The ARIMA and SARIMAX achieved a mean absolute percentage error 3.71% and 13.39%, respectively, in forecasting dispersion and movement. The proposed approach can serve as a solution for automatic monitoring of anomalous chicken dispersion and movement in chicken farming, alerting farmers of potential health risks and environmental hazards in chicken farms.

Inhibition of inflammation and infiltration of M2 macrophages in NSCLC through the ATF3/CSF1 axis: Role of miR-27a-3p.

Non-small cell lung cancer (NSCLC) imposes a significant economic burden on patients and society due to its low overall cure and survival rates. Tumour-associated macrophages (TAM) affect tumour development and may be a novel therapeutic target for cancer. We collected NSCLC and tumour-adjacent tissue samples. Compared with the tumour-adjacent tissues, the Activation Transcription Factor 3 (ATF3) and Colony Stimulating Factor 1 (CSF-1) were increased in NSCLC tissues. Levels of ATF3 and CSF-1 were identified in different cell lines (HBE, A549, SPC-A-1, NCI-H1299 and NCI-H1795). Overexpression of ATF3 in A549 cells increased the expression of CD68, CD206 and CSF-1. Moreover, levels of CD206, CD163, IL-10 and TGF-ß increased when A549 cells were co-cultured with M0 macrophages under the stimulation of CSF-1. Using the starbase online software prediction and dual-luciferase assays, we identified the targeting between miR-27a-3p and ATF3. Levels of ATF3, CSF-1, CD206, CD163, IL-10 and TGF-ß decreased in the miR-27a mimics, and the tumour growth was slowed in the miR-27a mimics compared with the mimics NC group. Overall, the study suggested that miR-27a-3p might inhibit the ATF3/CFS1 axis, regulate the M2 polarization of macrophages and ultimately hinder the progress of NSCLC. This research might provide a new therapeutic strategy for NSCLC.