Single-cell and spatial transcriptomics reveal apelin/APJ pathway's role in microvessel formation and tumour progression in hepatocellular carcinoma.

The apelin receptor (APJ) is a key player in tumour angiogenesis, but its role in hepatocellular carcinoma (HCC) remains unclear. This study aims to elucidate the function of the apelin/APJ pathway in HCC using a multi-omics approach and identify potential therapeutic biomarkers. Differentially expressed genes related to the apelin/APJ axis were identified from bulk transcriptomics to reveal HCC-associated disparities. Single-cell and spatial transcriptomics were used to localize and analyse the function of these genes. Machine learning models were constructed to predict outcomes based on apelin/APJ expression, and experimental validation was conducted to explore the pathway's impact on HCC angiogenesis. Single cell analysis revealed an overexpression of APJ/Aplin in the endothelium. The stemness of endothelial cell (EC) with high apelin/APJ was enhanced, as well as the expression of TGFb, oxidative stresses and PI3K/AKT pathway genes. Spatial transcriptomics confirmed that EC populations with high APJ scores were enriched within the tumour. Machine learning models showed high prognostic accuracy. High APJ expression was linked to worse outcomes (p = 0.001), and AUC values were high (1 year, 3 year, 5 year) (0.95, 0.97, 0.98). Immune suppression and non-responsiveness of immune therapy were also seen in high-risk groups. The experimental validation showed that silencing apelin reduced angiogenesis (p < 0.05), endothelial proliferation, decreased expression of ANG2, KLF2, VEGFA and lower ERK1/2 phosphorylation. Apelin may serve as a potential therapeutic target in HCC, given its role in promoting tumour angiogenesis and poor patient outcomes.

Berberine: Potential preventive and therapeutic strategies for human colorectal cancer.

Colorectal cancer (CRC) is a common digestive tract tumor, with incidences continuing to rise. Although modern medicine has extended the survival time of CRC patients, its adverse effects and the financial burden cannot be ignored. CRC is a multi-step process and can be caused by the disturbance of gut microbiome and chronic inflammation's stimulation. Additionally, the presence of precancerous lesions is also a risk factor for CRC. Consequently, scientists are increasingly interested in identifying multi-target, safe, and economical herbal medicine and natural products. This paper summarizes berberine's (BBR) regulatory mechanisms in the occurrence and development of CRC. The findings indicate that BBR regulates gut microbiome homeostasis and controls mucosal inflammation to prevent CRC. In the CRC stage, BBR inhibits cell proliferation, invasion, and metastasis, blocks the cell cycle, induces cell apoptosis, regulates cell metabolism, inhibits angiogenesis, and enhances chemosensitivity. BBR plays a role in the overall management of CRC. Therefore, using BBR as an adjunct to CRC prevention and treatment could become a future trend in oncology.

A meta-analysis of the efficacy and toxicity of tyrosine kinase inhibitors in treating patients with different types of thyroid cancer: how to choose drugs appropriately?

PURPOSE OF REVIEW: Because the high risk of death and poor prognosis of patients with refractory thyroid cancer (TC), studies related to tyrosine kinase inhibitors (TKIs) in treating different types of refractory TC have gradually attracted attention. Thus, we conducted a meta-analysis of published randomized controlled trials and single-arm trials to evaluate tyrosine kinase inhibitors' efficacy and safety profile treatment in TC patients. RECENT FINDINGS: The studies of 29 in 287 met the criteria, 9 were randomized controlled trials and 20 were single-arm trials, involving 11 TKIs (Apatinib, Anlotinib, Cabozantinib, Imatinib, Lenvatinib, Motesanib, Pazopanib, Sorafenib, Sunitinib, Vandetanib, Vemurafenib). Treatment with TKIs significantly improved progression-free survival [hazard ratio [HR] 0.34 (95% confidence interval [CI]: 0.24, 0.48), P < 0.00001] and overall survival [OS] [HR 0.76, (95% CI: 0.64, 0.91), P = 0.003] in randomized controlled trials, but adverse events (AEs) were higher than those in the control group (P < 0.00001). The result of the objective response rate (ORR) in single-arm trials was statistically significant [odds ratio [OR] 0.49 (95% CI: 0.32, 0.75), P = 0.001]. SUMMARY: TKIs significantly prolonged progression-free survival and OS or improved ORR in patients with different types of TC (P < 0.01). Our recommendation is to select appropriate TKIs to treat different types of TC patients, and to prevent and manage drug-related AEs after using TKIs.

Efficacy and safety of immune checkpoint inhibitors in colorectal cancer: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Immune checkpoint inhibitor (ICI) therapies have shown promising prospects in colorectal cancer (CRC) immunotherapy; many clinical trials have been carried out. In this study, we sought to evaluate the efficacy and safety of ICI therapies in CRC by presenting a meta-analysis of relevant studies. METHODS: Databases including PubMed, Embase, Cochrane Library, and Web of Science were systematically searched for studies concerning the efficacy and safety of ICI in colorectal cancer. The reported odds ratio (OR) or weighted mean difference (WMD) with 95% confidence intervals (CIs) of overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), treatment-related adverse events (TRAEs), and TRAEs ≥ 3 in the included studies were analyzed by fixed effects/random effects models. RESULTS: Three studies involving 667 patients with colorectal cancer were included in our meta-analysis. No significant difference between the immune checkpoint inhibitor therapies and conventional therapies in OS (WMD = 0.73, 95% CI - 3.09, 4.54; p = 0.71), in ORR (OR = 1.54, 95% CI 0.98, 2.40; p = 0.06), and in DCR (OR = 0.97, 95% CI 0.36, 2.61; p = 0.95). The median PFS of the ICI therapy group was shorter than that of the conventional therapy group (WMD = - 0.10, 95% CI - 0.18, - 0.02; p = 0.02). At the same time, we also could not find a significant difference between the immune checkpoint inhibitor therapies and conventional therapies in TRAEs (OR = 1.56, 95% CI 0.11, 22.09; p = 0.74) and in TRAEs ≥ 3 (OR = 0.94, 95% CI 0.16, 5.65; p = 0.95). CONCLUSION: Immune checkpoint inhibitor therapies could not improve all survival endpoints to advanced or metastatic colorectal cancer patients. Whether immune checkpoint inhibitors should be the first choice of therapies for colorectal cancer patients with undetermined microsatellite status or not able to determine microsatellite status needs more related studies to prove.

IGFBP7 contributes to epithelial-mesenchymal transition of HPAEpiC cells in response to radiation.

Radiation-induced lung injury (RILI) frequently occurs in patients with thoracic malignancies. In response to radiation, alveolar epithelial cells (AEC) undergo epithelial-mesenchymal transition (EMT) and contribute to the pathogenesis of RILI. Insulin-like growth factor binding protein 7 (IGFBP7) is reported as a downstream mediator of transforming growth factor-ß1 (TGF-ß1) pathway, which plays a crucial role in radiation-induced EMT. In the present study, the levels of IGFBP7 and TGF-ß1 were simultaneously increased in experimental RILI models and radiation-treated AEC (human pulmonary alveolar epithelial cells [HPAEpic]). The expression of IGFBP7 in radiation-treated HPAEpic cells was obviously inhibited by the specific inhibitor of TGF-ß receptor antagonist SB431542 and TGF-ß1 neutralizing antibody, and time-dependently enhanced by TGF-ß1 treatment. Moreover, IGFBP7 knockdown significantly attenuated the effects of radiation on morphology change, cell migration, expression of EMT-related markers (E-cadherin, α-SMA, and Vimentin), and phosphorylation of extracellular-signal-regulated kinase (ERK). The effects of IGFBP7 overexpression on the expression of EMT-related markers were partially reversed by the ERK inhibitor PD98059. In conclusion, IGFBP7, was enhanced by TGF-ß1, may be involved in radiation-induced EMT of AEC via the ERK signaling pathway, thus contributing to the pathogenesis of RILI.

Radiation Enhances the Epithelial- Mesenchymal Transition of A549 Cells via miR3591-5p/USP33/PPM1A.

BACKGROUND/AIMS: Radiotherapy plays a critical role in lung cancer treatment. Radiation can activate transforming growth factor-ß (TGF-ß) signaling and induce the epithelial-mesenchymal transition (EMT), which may lead to distant metastases. MicroRNAs (miRNAs) have been suggested to affect radiotherapy in lung cancer. METHODS: miRNA Next-Generation Sequencing was performed to investigate the effects of irradiation on the miRNA profile of lung cancer A549 cells. The functions of identified miRNA on the radiation induced EMT and TGF-ß activation in A549 cells were then explored. Protein expression was evaluated by western blotting. Immunofluorescence staining was performed to detect the localization of Snail. Luciferase Assay was used to determine the target gene regulated by the identified miRNA. RESULTS: Radiation time-dependently induced EMT in A549 lung cancer cells as indicated by the changes of morphology, the expression of EMT marker proteins (E-cadherin, α-SMA and Vimentin) and the nuclear localization of Snail. Moreover, miR-3591-5p was identified as the most significant increased miRNA in response to radiation, and further experiments indicated that miR-3591-5p was required for radiation induced EMT and TGF-ß/ Smad2/3 activation. Ubiquitin Specific Peptidase 33 (USP33) was a downstream target of miR-3591-5p as predicted by TargetScan and validated by 3' untranslated regions (UTRs) Luciferase Assay. USP33 could deubiquitinate PPM1A (protein phosphatase, Mg2+/Mn2 + dependent 1A), a phosphatase for Smad2/3. Ectopic expression of USP33 or PPM1A partially abolished the effects of miR-3591-5p on EMT and TGF-ß/ Smad2/3 activation. CONCLUSION: The present study revealed the critical role of miR-3591-5p/USP33/PPM1A in radiation-induced EMT via TGF-ß signaling and may suggest novel radiation sensitise strategies for lung cancer.

[Adjuvant function of guilu erxian glue cataplasm in treating carcinoma of the large intestine patients with myelosuppression after chemotherapy: a clinical observation].

OBJECTIVE: To observe the clinical effect of Guilu Erxian Glue Cataplasm (GEGC) on carcinoma of the large intestine patients with myelosuppression after chemotherapy, and further to confirm its efficiency and safety. METHODS: Totally 60 patients with carcinoma of the large intestine were randomly assigned to two groups. Meanwhile, they all accepted FOLFIRI chemotherapy. Patients in the treatment group were additionally applied at Shenque (RN8), exchanging once per every other day, for 14 successive days. Patients in the control group took placebos with the same dose and dosage as the treatment group. The blood cell counts (WBC, NE, and PLT) were detected before chemotherapy, at day 7, 10, and 14. The TCM symptoms integrals, Karnofsky performance score (KPS), liver and kidney functions were observed before chemotherapy, at day 7 and day 14. Adverse skin reactions were observed each day. And the usage of hematopoietic growth factors was recorded. RESULTS: (1) The KPS score at day 7 was more stable in the treatment group than in the control group; the WBC and NE counts in the peripheral blood at day 14 were higher in the treatment group than in the control group; and TCM symptoms integrals at day 14 was lower in the treatment group than in the control group, all with statistical difference (P < 0.05). (2) Compared with the control group, the PLT count was higher in the treatment group than in the control group, the usage of rhG-CSF and antibiotics was less in the treatment group than in the control group, all with no statistical difference (P > 0.05). (3) No obvious adverse reactions such as liver injury, renal injury, or skin allergy were observed. CONCLUSIONS: Adjuvant treatment of GEGC could improve carcinoma of the large intestine patients with myelosuppression to some extent. No relevant adverse reactions were found.

Mesenchymal stem cell-derived exosomes as delivery vehicles for non-coding RNAs in lung diseases.

The burden of lung diseases is gradually increasing with an increase in the average human life expectancy. Therefore, it is necessary to identify effective methods to treat lung diseases and reduce their social burden. Currently, an increasing number of studies focus on the role of mesenchymal stem cell-derived exosomes (MSC-Exos) as a cell-free therapy in lung diseases. They show great potential for application to lung diseases as a more stable and safer option than traditional cell therapies. MSC-Exos are rich in various substances, including proteins, nucleic acids, and DNA. Delivery of Non-coding RNAs (ncRNAs) enables MSC-Exos to communicate with target cells. MSC-Exos significantly inhibit inflammatory factors, reduce oxidative stress, promote normal lung cell proliferation, and reduce apoptosis by delivering ncRNAs. Moreover, MSC-Exos carrying specific ncRNAs affect the proliferation, invasion, and migration of lung cancer cells, thereby playing a role in managing lung cancer. The detailed mechanisms of MSC-Exos in the clinical treatment of lung disease were explored by developing standardized culture, isolation, purification, and administration strategies. In summary, MSC-Exo-based delivery methods have important application prospects for treating lung diseases.

Efficacy and safety of neoadjuvant combination immunotherapy in surgically resectable malignant solid tumors: a systematic review and meta-analysis.

OBJECTIVES: Neoadjuvant immunotherapy has emerged as a prominent research focus recently. For potentially operable patients, neoadjuvant therapy serves as a primary method to reduce tumor load and facilitate surgical interventions. METHODS: We retrieved articles from PubMed, Embase, Cochrane Library, American Society of Clinical Oncology, and European Society of Medical Oncology websites from inception to December 2023. Statistical analyses were performed using the R software. Primary outcomes assessed included major pathological response (MPR), pathological complete response (pCR), and treatment-related adverse events (trAEs). RESULTS: 29 studies encompassing 1163 patients were included. The MPR rate of neoadjuvant combination immunotherapy was 38% (95% confidence interval [CI]: 25%-52%), and the pCR rate was 33% (95%CI: 25%-42%). These values were significantly higher than those obtained with single agent immunotherapy (p < 0.001). The pooled incidence of overall trAEs was 83% (95%CI: 73%-92%), and grade (G) 3-4 trAEs was 22% (95%CI: 15%-29%), both significantly higher than those observed with single agent immunotherapy (p < 0.05). CONCLUSION: This study demonstrated the efficacy of neoadjuvant combination immunotherapy. Given that the majority of the included trials were phase II with small sample sizes, further multicenter phase III randomized controlled trials should be conducted to validate the findings of the review.

Comparative efficacy and safety of cabozantinib for malignant tumors: a systematic review and meta-analysis.

OBJECTIVES: To provide a more comprehensive understanding of the efficacy and safety profile of cabozantinib versus placebo in malignant tumors, we conducted a systematic review and meta-analysis. This involved analyzing a collection of published randomized controlled trials to assess the outcomes. METHODS: We used RevMan5.3 software to evaluate the outcomes of the collected studies. The primary outcome we focused on was progression-free survival (PFS), and the secondary outcomes included overall survival (OS) and disease control rate (DCR). RESULTS: Our findings revealed that compared to placebo, cabozantinib significantly extended the PFS of patients [hazard ratios (HR) 0.37, 95% confidence intervals (CI): 0.32, 0.43, p < 0.00001]. Additionally, cabozantinib improved the OS of patients [HR 0.78, 95%CI: 0.68, 0.91, p = 0.002]. While it is important to note that cabozantinib was associated with a higher likelihood of causing digestive, cutaneous, and cardiovascular related adverse events [relative risk (RR) 4.40, 95% CI: 3.10, 6.25, p < 0.00001]. CONCLUSION: Based on our analysis, cabozantinib significantly prolonged the PFS and OS of patients with malignant tumors (p < 0.01). We recommend the use of cabozantinib in treating advanced malignant tumors. However, it is important to continuously monitor and manage the drug-related adverse events. REGISTRATION: PROSPERO (No. CRD42023449261).

Leveraging molecular targeted drugs and immune checkpoint inhibitors treat advanced thyroid carcinoma to achieve thyroid carcinoma redifferentiation.

Thyroid cancer can be classified into three different types based on the degree of differentiation: well-differentiated, poorly differentiated, and anaplastic thyroid carcinoma. Well-differentiated thyroid cancer refers to cancer cells that closely resemble normal thyroid cells, while poorly differentiated and anaplastic thyroid carcinoma are characterized by cells that have lost their resemblance to normal thyroid cells. Advanced thyroid carcinoma, regardless of its degree of differentiation, is known to have a higher likelihood of disease progression and is generally associated with a poor prognosis. However, the process through which well-differentiated thyroid carcinoma transforms into anaplastic thyroid carcinoma, also known as "dedifferentiation", has been a subject of intensive research. In recent years, there have been significant breakthroughs in the treatment of refractory advanced thyroid cancer. Clinical studies have been conducted to evaluate the efficacy and safety of molecular targeted drugs and immune checkpoint inhibitors in the treatment of dedifferentiated thyroid cancer. These drugs work by targeting specific molecules or proteins in cancer cells to inhibit their growth or by enhancing the body's immune response against the cancer cells. This article aims to explore some of the possible mechanisms behind the dedifferentiation process in well-differentiated thyroid carcinoma. It also discusses the clinical effects of molecular targeted drugs and immune checkpoint inhibitors in thyroid cancer patients with different degrees of differentiation. Furthermore, it offers insights into the future trends in the treatment of advanced thyroid cancer, highlighting the potential for improved outcomes and better patient care.

Identification of KRT80 as a Novel Prognostic and Predictive Biomarker of Human Lung Adenocarcinoma via Bioinformatics Approaches.

BACKGROUND: According to the 2022 Global Cancer Statistics, lung cancer is the leading cause of cancer-related mortality worldwide. Lung adenocarcinoma (LUAD), which is a histological subtype of Non- Small Cell Lung Cancer (NSCLC), accounts for 40% of primary lung cancer. Therefore, there is an urgent need to identify new prognostic markers as clinical predictive markers for LUAD. OBJECTIVE: This study aimed to investigate the role of Keratin 80 (KRT80) in the prognosis of LUAD and its underlying mechanisms. METHODS: Bioinformatics analysis was conducted using data retrieved from The Cancer Genome Atlas (TCGA) databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were employed to predict the involved biological processes and signaling pathways, respectively. The LinkedOmics database was utilized to identify differentially expressed genes (DEGs) correlated with KRT80. Nomograms and Kaplan-Meier plots were constructed to evaluate the survival outcomes of patients diagnosed with LUAD. Moreover, TIMER was employed to conduct correlation analyses between KRT80 expression and immune cell infiltration, shedding light on the intricate interplay between KRT80 and the tumor microenvironment in LUAD. To ascertain the RNA and protein expression levels of KRT80 in LUAD and adjacent normal tissues, Reverse Transcription-quantitative Polymerase Chain Reaction (RT-qPCR) and immunohistochemistry techniques were employed, respectively. RESULTS: Scrutiny of the TCGA dataset revealed KRT80 up-regulation across pan-cancer tissues, notably elevated in LUAD compared to healthy lung tissues. This finding was validated in our clinical samples, where Kaplan-Meier survival curves indicated poorer survival rates for high KRT80 expression in LUAD. A positive correlation was found between the transcription level of KRT80 in LUAD samples and clinical parameters, such as lymph node metastasis stage, distant metastasis, and pathological stage. Survival, logistic regression, and Cox regression analyses emphasized the clinical prognostic significance of high KRT80 expression in LUAD. Nomogram results underscored the robust predictive potential of KRT80 for the survival of LUAD patients. Gene functional enrichment analyses mainly associated KRT80 with cytokine-cytokine receptor interactions, cell cycle, apoptosis, and chemokine signaling pathways. Based on the results of the immune infiltration analysis, it can be found that the expression of KRT80 is related to the immune cell subsets and survival rate of patients with LUAD. CONCLUSION: Our research revealed a significant upregulation of KRT80 in LUAD, with heightened KRT80 expression correlating with unfavorable prognosis. This study represents a comprehensive and systematic evaluation of KRT80 expression in LUAD, encompassing its prognostic and diagnostic significance, as well as underlying mechanisms. Our findings suggest that KRT80 may emerge as a novel prognostic and predictive biomarker in LUAD.

Cabozantinib in combination with immune checkpoint inhibitors for renal cell carcinoma: a systematic review and meta-analysis.

Context: Cabozantinib combined with immune checkpoint inhibitors (ICIs) has brought a new therapeutic effect for the medical treatment of renal cell carcinoma (RCC). Objectives: We performed a meta-analysis of randomized controlled trials and single-arm trials to evaluate the efficacy and safety of cabozantinib plus ICIs in RCC. Methods: We extracted data from PubMed, Cochrane, Medline and Embase databases, and rated literature quality through Cochrane risk of bias tool and MINORS. RevMan5.3 software was used to analyze the results of randomized controlled trials and single-arm trials. Results: A total of 7 studies were included. Treatment with cabozantinib plus ICIs improved PFS [HR 0.75, (95%CI: 0.52, 1.08), p = 0.12] and the OS [HR 0.80, (95%CI: 0.60, 1.07), p = 0.13] in randomized controlled trials. Meanwhile, the result of the ORR in randomized controlled trials was [risk ratio (RR) 1.37, (95%CI: 1.21, 1.54), p < 0.00001] and in single-arm trials was [risk difference (RD) 0.49, (95%CI: 0.26, 0.71), p < 0.0001]. Conclusion: Cabozantinib plus ICIs prolonged the PFS and OS, and improved ORR in patients with RCC. Our recommendation is to use cabozantinib plus ICIs to treat advanced RCC, and to continuous monitor and manage the drug-related adverse events. Systematic Review Registration: identifier CRD42023455878.

[Retrospective study on the dynamic development of Chinese medical syndrome types of gastric cancer].

OBJECTIVE: To observe the effects of surgery and chemotherapy on the development of Chinese medical syndrome types on patients with gastric cancer (GC), thus providing the evidence for treating GC by Chinese medical syndrome differentiation and treatment by stages. METHODS: A retrospective study was carried out in 500 GC patients according to before and after surgery, the surgical ways, before and after chemotherapy to observe the dynamic development of Chinese medical syndrome types of GC. RESULTS: Pi deficiency syndrome dominated in GC patients of single syndrome or two syndromes before and after surgery. After surgery (after radical resection or palliative resection) Pi deficiency syndrome and blood deficiency syndrome significantly increased. There was statistical difference in syndrome type changes before and after chemotherapy (P < 0.05). CONCLUSIONS: Deficiency syndrome mainly dominated in GC patients. They should be treated by stages when Chinese medicine and pharmacy took part in its treatment.

Adverse events of neoadjuvant combination immunotherapy for resectable cancer patients: a systematic review and meta-analysis.

Background: Neoadjuvant combination immunotherapy is changing the treatment landscape for patients with cancer. Exploring the incidence of immune-related adverse events (irAEs) in relation to this novel approach may provide valuable insights for future clinical investigations. Methods: This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Embase, Cochrane Library, American Society of Clinical Oncology (ASCO), and European Society of Medical Oncology (ESMO) websites were searched for all relevant literature from their inception to November 24, 2023. We then extracted the required data from the included studies and used the R software to analyze the pooled incidence of irAEs. Subgroup analyses examined the pooled incidence of irAEs according to cancer and combination types using a random-effects model. Results: Sixteen studies involving 501 patients were included in the meta-analysis. Considering the heterogeneity of the study design, we analyzed the randomized controlled studies (RCTs) and the single-arm studies separately. In RCTs, the incidence of any-grade irAEs was 95.0% (95% confidence interval [CI] 87.3-99.3) and that of grade ≥3 irAEs was 24.0% (95% CI 13.7-36.0). In single-arm studies, the incidence of any-grade irAEs was 89.4% (95% CI 75.0-98.0) and grade ≥3 irAEs was 20.3% (95% CI 8.7-35.2). In both RCTs and single arms, the most common any- grade irAEs were rash and fatigue, while the most common grade ≥3 irAEs was abnormal liver function and colitis. Due to irAEs, 9.4% of patients in RCTs and 6.9% of patients in single-arm studies did not complete the prescribed neoadjuvant treatment cycle. Conclusion: This study comprehensively summarized the incidence of irAEs in neoadjuvant combination immunotherapy. The occurrence of irAEs varies depending on the cancer and combination types. Our meta-analysis provides clinicians with essential guidance for the management of patients with cancer. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42023387969.

Heterogeneous aggregation between microplastics and microalgae: May provide new insights for microplastics removal.

Existing studies have shown that microplastics (MPs) as artificial surfaces can be colonized by plankton microorganisms. However, systematic research on exploring the aggregation formation process of MPs and microalgae is still lacking and particularly the influencing factors of aggregation remain to be elucidated. Therefore, this study investigated the heterogeneous aggregation process between various microalgal species (i.e., Chlorella vulgaris, Scenedesmus obliquus, Tetraselmis subcordiformis, Chaetoceros müelleri and Streptococcus westermani) and MPs (i.e., mPS and mPLA) with different sizes (i.e., 74 µm and 613 µm), concentrations (i.e., 0.1 g/L, 1 g/L and 2 g/L) and shapes (i.e., the particle and sheet). The results showed that microalgae can first attach to the holes or protrusions of MPs and highly accumulate in the local region, and then multi-layer aggregation can be formed subsequently. The aggregation degree between MPs and microalgae was closely related to the MPs shape and size, and was less related to the MPs concentration. The aggregation speed of small-sized MPs (e.g., 74 µm) was faster than the large-sized ones (e.g., 613 µm). The MPs in a shape of sheet were more obvious than those in particle on their aggregation with microalgae. The density of aggregates was increased compared with pristine MPs, which is related to the cell density and cell number of attached microalgae. For the same type of MPs, the aggregation degree for the tested microalgae was as follows: Scenedesmus obliquus > C. vulgaris > T. subcordiformis > C. müelleri > S. westermani. Meanwhile, MPs inhibited cell growth of microalgae, particularly under the circumstance of their aggregation, by limiting the gas and mass transfer between microalgal cells and the extracellular environment. The heterogeneous aggregation of MPs and microalgae may provide new ideas for treatment and controlling of MPs in the environment.

Efficacy and safety of HER2-targeted therapy in patients with colorectal cancer: What should we expect from a meta-analysis?

BACKGROUND AND OBJECTIVE: Human epidermal growth factor receptor 2 (HER2) is an effective therapeutic target for breast and stomach cancers. However, the application of HER2-targeted therapy in colorectal cancer (CRC) remains controversial. We sought to assess the efficacy and safety of HER2-targeted therapy in CRC by performing a meta-analysis of relevant studies. METHODS: We searched PubMed, Embase, Cochrane Library, Web of Science, and the ClinicalTrials.gov database to retrieve relevant studies. STATA 16 was used for the statistical analysis. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and incidence of treatment­related adverse events (TRAEs) were used as the outcome indicators analyzed by random- or fixed-effects models. RESULTS: A total of 267 patients from nine studies were included in this meta-analysis. The overall ORR and DCR were 27.5% (95% CI 16.8% to 39.6%) and 68.9% (95% CI 55.4% to 81.0%), respectively. No significant heterogeneity was found in PFS among these studies and the overall median PFS was 4.35 months (95% CI 3.70 to 4.99). The overall incidence of all-grade and grade 3 or higher adverse events were 93.5% (95% CI 88.4% to 97.4%) and 16.8% (95% CI 4.8% to 33.3%). CONCLUSIONS: HER2-targeted therapy was confirmed as a promising treatment for colorectal cancer, warranting further high-quality clinical randomized controlled trials to verify.

Identification of CDT1 as a prognostic marker in human lung adenocarcinoma using bioinformatics approaches.

Background: Lung cancer has the highest cancer-related mortality worldwide. Lung adenocarcinoma (LUAD) is the most common histological subtype of non-small cell lung cancer (NSCLC). Chromatin licensing and DNA replication factor 1 (CDT1), a key regulator of cell cycle control and replication in eukaryotic cells, has been implicated in various cancer-related processes. Given its significant role in cancer, the focus on CDT1 in this study is justified as it holds promise as a potential biomarker or therapeutic target for cancer treatment. However, its prognostic value in lung adenocarcinoma (LUAD) remains unclear. Methods: Bioinformatics analysis was conducted using data obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were utilized to predict biological processes and signaling pathways, respectively. The LinkedOmics database was employed to identify differentially expressed genes (DEGs) associated with CDT1. Nomograms and Kaplan-Meier plots were generated to assess the survival rates of patients with lung adenocarcinoma (LUAD). To determine the RNA and protein expression levels of CDT1 in LUAD and adjacent normal tissues, quantitative polymerase chain reaction (qPCR) and immunohistochemistry techniques were employed, respectively. Results: CDT1 was upregulated in the vast majority of cancer tissues, based on pan-cancer analysis in TCGA and GEO datasets, as to lung cancer, the level of CDT1 expression was much higher in LUAD tissue than in healthy lung tissue. Our clinical data supported these findings. In our study, we used a specific cutoff value to dichotomize the patient samples into high and low CDT1 expression groups. The Kaplan-Meier survival curve revealed poor survival rates in CDT1 high expression group than the low expression group. To determine if CDT1 expression was an independent risk factor in LUAD patients, univariate and multivariate Cox regression analyses were performed. The result showed that CDT1 was a potential novel prognosis factor for LUAD patients, whose prognosis was poorer when CDT1 expression was higher. Based on functional enrichment analysis, highly expressed DEGs of CDT1-high patients were predicted to be involved in the cell cycle. According to our analysis of immune infiltration, CDT1 exhibited a strong correlation with specific immune cell subsets and was found to be a significant predictor of poor survival in patients with LUAD. Conclusions: Our research found that CDT1 was upregulated in LUAD and that high CDT1 expression predicted poor prognosis. We comprehensively and systematically analyzed the expression level in the datasets as well as in our own clinical samples, we also evaluated the prognostic and diagnostic value of CDT1, and finally, the potential mechanisms of CDT1 in the progression of LUAD. These results suggested that CDT1 may be a prognostic marker and therapeutic target for LUAD.

Biodegradable and conventional microplastics posed similar toxicity to marine algae Chlorella vulgaris.

It has been demonstrated that some conventional microplastics (CMPs) have toxicities to organisms, however, whether biodegradable microplastics (BMPs) have similar potential risks to marine ecosystems remains to be elucidated. Therefore, this study aimed to investigate i) the effects of CMPs (i. e., micro-sized polyethylene (mPE) and polyamide (mPA)) on marine algae Chlorella vulgaris; and ii) the potential effects of BMPs (i.e., micro-sized polylactic acid (mPLA) and polybutylene succinate (mPBS)) on C. vulgaris. The results showed that either CMPs or BMPs inhibited the growth of microalgae compared with the control. The maximum inhibition ratio of the four types of MPs on C. vulgaris were 47.24% (mPE, 1 000 mg/L), 40.36% (mPA, 100 mg/L), 47.95% (mPLA, 100 mg/L) and 34.25% (mPBS, 100 mg/L), respectively. Among them, mPLA showed the strongest inhibitory effect on the growth of C. vulgaris. Interestingly, the MPs can stimulate the contents of pigments (e.g., chlorophyll a, chlorophyll b, and carotenoid), which may be acted as cellular defense to the stress induced by MPs. The results also showed that MPs stimulated the production of EPS. Under the investigated condition, the strongest inhibition on C. vulgaris was induced by mPLA, and followed by mPE, mPA, and mPBS. It was found that the factors such as the physicochemical properties of MPs (e.g., shading effect, the roughness of surface, the increase in potential), the chemical changes (i.e., the release of additives, the increase of oxidative stress) contributed to the inhibitory effects of MPs on microalgae, but the deciding factor remains to be further systematically explored.