Comparison of clopidogrel and ticagrelor in treating acute coronary syndrome undergoing PCI: A systematic review and meta-analysis.

Objective: The study aims to evaluate and compare the efficacy and safety between ticagrelor and clopidogrel in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). Methods: We searched MEDLINE (via PubMed), Cochrane, Embase, and the Cochrane library databases for eligible citations (the last search was up to December 2021). Subgroup analyses were performed based on region, study design, dose, and single-center/multicenter. Meta regressions were conducted to explore the source of heterogeneity. A sensitivity analysis was conducted to assess the robustness of the results. Funnel plots and Egger's test were preformed to test publication bias of the meta-analysis. Results: A total of 29 studies were included, totaling 165,981 patients. Ticagrelor reduced the overall incidence rate of major adverse cardiovascular events (MACEs) (HR 0.74; 95% CI, 0.62, 0.89; P = 0.001; I2 = 88.3%, P < 0.001) and all-cause mortality (HR 0.85; 95% CI, 0.75, 0.97; P = 0.019; I2 = 39.7%, P = 0.052) compared with clopidogrel. However, there was a higher risk of major bleeding (HR 1.21; 95% CI, 1.02,1.44; P = 0.026, I2 = 59.3%, P = 0.012) and all bleeding (HR 1.42; 95% CI, 1.24, 1.62; P < 0.001, I2 = 76.4%, P < 0.001) with ticagrelor compared to clopidogrel. The stability of the results was demonstrated by sensitivity analysis. Furthermore, subgroup analyses and meta-regression revealed that the heterogeneity in the study may stem from factors such as whether it was conducted in a single-center or multicenter setting, as well as the geographical region. Conclusion: Ticagrelor has demonstrated superior efficacy compared to clopidogrel in ACS patients undergoing PCI, particularly in Asia and Europe. Nevertheless, it is crucial to acknowledge that the utilization of ticagrelor is linked to a heightened risk of bleeding. To provide guidance for clinical decision-making regarding the use of ticagrelor, future multicenter randomized trials that are relevant and encompass longer follow-up periods are necessary. The category of the manuscript a meta-analysis: PROSPERO registration number CRD42021274198.

Whole-tumor histogram analysis of synthetic magnetic resonance imaging predicts isocitrate dehydrogenase mutation status in gliomas.

Background: An accurate assessment of isocitrate dehydrogenase (IDH) status in patients with glioma is crucial for treatment planning and is a key factor in predicting patient outcomes. In this study, we investigated the potential value of whole-tumor histogram metrics derived from synthetic magnetic resonance imaging (MRI) in distinguishing IDH mutation status between astrocytoma and glioblastoma. Methods: In this prospective study, 80 glioma patients were enrolled from September 2019 to June 2022. All patients underwent pre- and post-contrast synthetic MRI scan protocol. Immunohistochemistry (IHC) staining or gene sequencing were used to assess IDH mutation status in tumor tissue samples. Whole-tumor histogram metrics, including T1, T2, proton density (PD), etc., were extracted from the quantitative maps, while radiological features were assessed by synthetic contrast-weighted maps. Basic clinical features of the patients were also evaluated. Differences in clinical, radiological, and histogram metrics between IDH-mutant astrocytoma and IDH-wildtype glioblastoma were analyzed using univariate analyses. Variables with statistical significance in univariate analysis were included in multivariate logistic regression analysis to develop the combined model. Receiver operating characteristic (ROC) and area under the curve (AUC) were used to assess the diagnostic performance of metrics and models. Results: The histopathologic analysis revealed that of the 80 cases, 41 were classified as IDH-mutant astrocytoma and 39 as IDH-wildtype glioblastoma. Compared to IDH-wildtype glioblastoma, IDH-mutant astrocytoma showed significantly lower T1 [10th percentile (10th), mean, and median] and post-contrast PD (10th, 90th percentile, mean, median, and maximum) values as well as higher post-contrast T1 (cT1) (10th, mean, median, and minimum) values (all P<0.05). The combined model (T1-10th + cT1-10th + age) was developed by integrating the independent influencing factors of IDH-mutant astrocytoma using the multivariate logistic regression. The diagnostic performance of this model [AUC =0.872 (0.778-0.936), sensitivity =75.61%, and specificity =89.74%] was superior to the clinicoradiological model, which was constructed using age and enhancement degree (AUC =0.822 (0.870-0.898), P=0.035). Conclusions: The combined model constructed using histogram metrics derived from synthetic MRI could be a valuable preoperative tool to distinguish IDH mutation status between astrocytoma and glioblastoma, and subsequently, could assist in the decision-making process of pretreatment.

A Differential Protein Study on Bronchoalveolar Lavage Fluid at Different Stages of Silicosis.

OBJECTIVES: In this study, by comparing the difference in protein expression in bronchoalveolar lavage fluid between silicosis patients in different stages and healthy controls, the pathogenesis of pneumoconiosis was discussed, and a new idea for the prevention and treatment of pneumoconiosis was provided. METHODS: The lung lavage fluid was pretreated by 10 K ultrafiltration tube, Agilent 1100 conventional liquid phase separation, strong cation exchange column (SCX) HPLC pre-separation, and C18 reverse phase chromatography desalting purification, and protein was labeled with isotope. GO, KEGG pathway, and PPI analysis of differential proteins were conducted by bioinformatics, and protein types and corresponding signal pathways were obtained. RESULTS: Thermo Q-Exactive mass spectrometry identified 943 proteins. T-test analysis was used to evaluate the different significance of the results, and the different protein of each group was obtained by screening with the Ratio≥1.2 or Ratio≤0.83 and P<0.05. We found that there are 16 kinds of protein throughout the process of silicosis. There are different expressions of protein in stages Ⅲ/control, stages Ⅱ/control, stage Ⅰ/control, stages Ⅲ/ stages Ⅱ, stages Ⅲ/ stage Ⅰ and stages Ⅱ/ stage Ⅰ groups. The results of ontology enrichment analysis of total differential protein genes show that KEGG pathway enrichment analysis of differential protein suggested that there were nine pathways related to silicosis. CONCLUSION: The main biological changes in the early stage of silicosis are glycolysis or gluconeogenesis, autoimmunity, carbon metabolism, phagocytosis, etc., and microfibril-associated glycoprotein 4 may be involved in the early stage of silicosis. The main biological changes in the late stage of silicosis are autoimmunity, intercellular adhesion, etc. Calcium hippocampus binding protein may participate in the biological changes in the late stage of silicosis. It provides a new idea to understand the pathogenesis of silicosis and also raises new questions for follow-up research.

Dynamic simulation of the water-land-food nexus for the sustainable agricultural development in the North China Plain.

Inter-regional trade of agricultural products based on the flow of agricultural virtual resources is of great importance for sustainable agricultural development. We focused on grain crops (rice, wheat and maize) in the North China Plain (NCP), and used the Penman-Monteith equation to simulate crop water requirements. We further analyzed the flow of virtual land and virtual water associated with the grain trade using an environmentally expanded multi-regional input-output model. The coupling coordination of land, water, and food was evaluated to assess the rationality of regional agricultural production resource allocation. Between 2007 and 2017, agricultural virtual land and virtual water embodied in the grain trade between the NCP and other areas increased by 48.10 % and 34.41 %, respectively, indicating that the NCP is gradually consolidating its position as the main production area and distribution center of crops in China. Agricultural virtual resources in the NCP were mainly transported to the southeast coastal region, with an overall trend of resource movement from north to south. The total supply of agricultural land and water resources markedly increased in the NCP, whereas the transfer of virtual resources across regions showed a decreasing trend. Because of the irrational structure of crop cultivation and unevenness of regional resource allocation, the coupling coordination of the water-land-food nexus in the NCP is much lower than the national average. This study provides important information on the trade flows and coupling relationships of virtual water and land resources of three major food crops, which will help to alleviate resource pressure in agricultural production and promote sustainable agricultural development in the NCP.

Tele-connecting local consumption to cultivated land use and hidden drivers in China.

China faces significant pressure on cultivated land resources due to the accelerated pace of urbanization in recent years. The study of embodied cultivated land offers a new perspective on alleviating pressure on cultivated land between different regions. However, the temporal dynamics characteristic and the intersectoral linkages of embodied cultivated land have rarely been systematically described. Therefore, we applied an environmental extended multi-regional input-output approach to analyze the spatial patterns and flow relationships of virtual cultivated land (VCL) between regional, provincial and sectoral scale in China from 2007 to 2017, considering both temporal and spatial dimensions. Then, we explored the hidden drivers of VCL change using structural decomposition analysis (SDA). Our results showed that trade embodied cultivated land increase by 8.5 % from 2007 to 2017. The flow trend is primarily flowed out from the less developed northwest China but with abundant cultivated land to the more developed regions of the southeast coast. Especially, in 2015, the net outflow of VCL from the northwest region reached 15.82 Mha, which was the maximum value during the study period. In addition, agricultural and construction sector were the major land consumption sector. VCL consumed by the agricultural sector declined 12.51 %, while the VCL consumed by construction sector had a significant growth in 2007-2017. Furthermore, the results of SDA revealed that cultivated land use intensity and per capita final demand were the main factors causing changes in embodied cultivated land. The results can help clarify the responsible parties for land consumption and provide a guarantee for alleviating the pressure on regional cultivated land resources.

Association between the number of retrieved lymph nodes and demographic/tumour-related characteristics in colorectal cancer: a systematic review and meta-analysis.

OBJECTIVE: Clinical practice guidelines recommend retrieving at least 12 lymph nodes for correct staging in colorectal cancer. However, it is difficult to retrieve adequate lymph nodes because of various factors. We aimed to evaluate the association between the number of retrieved lymph nodes and demographic/tumour-related characteristics in colorectal cancer. DESIGN: Systematic review and meta-analysis of primary studies. DATA SOURCES: PubMed, Embase, Cochrane and Web of Science were searched from January 2016 to June 2023. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies that evaluated the association between retrieved lymph nodes and demographic/tumour-related characteristics in colorectal cancer were included. DATA EXTRACTION AND SYNTHESIS: OR with 95% conference intervals was extracted and pooled. RESULTS: A total of 54 studies containing 2 05 821 patients were included in this meta-analysis. The results showed that fewer nodes were retrieved from elderly patients (OR=0.70, 95% CI (0.54 to 0.90), p=0.005), and from tumours located in the left colon than in the right colon (OR=0.43, 95% CI (0.33 to 0.56), p<0.001). More lymph nodes were obtained from females than males (OR=1.15, 95% CI (1.04 to 1.28), p=0.006), from the advanced T stage (T3+T4) than T1+T2 stage (OR=1.57, 95% CI (1.25 to 1.97), p<0.001) and from the N2 stage than N0 stage (OR=1.32, 95% CI (1.15 to 1.51), p<0.001). Body mass index, ethnicity, N1 stage, M stage, tumour differentiation and lymph-vascular invasion were not significantly associated with the lymph node yield. CONCLUSIONS: The study results suggest that clinicians have an increased opportunity to retrieve sufficient lymph nodes for accurate pathological staging to guide treatment decisions in patients with colorectal cancer who are young, female, with tumours located in the right colon, advanced T stage and N2 stage.

Prognostic value of Interleukin-36s in cancers: A systematic review and meta-analysis.

BACKGROUND: Interleukin-36s (IL-36s) are a category of inflammatory cytokines and an increasing number of studies over the past decade have found that different kinds of IL-36s play different roles in cancers. This systematic review and meta-analysis aimed to evaluate the prognostic value of IL-36s in different cancer types. METHOD: Two reviewers independently searched in PubMed, Cochrane Library and EMBASE up to December 13, 2022. We extracted the hazard ratio (HR) and the confidence intervals (CIs) of the related prognostic outcomes and analyzed the pooled HR. RESULTS: We included 12 studies including 1925 patients. In all, six studies including IL-36α, five including IL-36γ and one including IL-36ß. A high expression of IL-36α was associated with better overall survival (OS) (HR = 0.48, 95 %CI: 0.37-0.62, P < 0.001) of cancer patients. The expression of IL-36γ was not related with cancers. Further, subgroup analysis showed that the expression of IL-36γ had no correlation with the OS of colorectal cancer (CRC) and non­small cell lung cancer (NSCLC) patients. Interestingly, a high expression of IL-36γ played contrasting prognostic roles in hepatocellular carcinoma (HCC) (HR = 0.43, 95 %CI: 0.27-0.69, P < 0.001) patients and gastric cancer (GC) (HR = 1.58, 95 %CI: 1.33-1.87, P < 0.001) patients. The only IL-36ß related study showed the expression of IL-36ß was not correlated with the prognosis of CRC patients (P > 0.05). CONCLUSION: IL-36α, IL-36ß and IL-36γ possibly play different roles in different cancers. High expression of IL-36α may be associated with good prognostic value in cancer patients, especially in CRC patients. The association between cancers prognosis and expression of IL-36ß or IL-36γ needs further evaluation. These conclusions need more clinical prognostic data for confirmation.

Photodynamic therapy improves the outcome of immune checkpoint inhibitors via remodelling anti-tumour immunity in patients with gastric cancer.

BACKGROUND: Photodynamic therapy (PDT) plays an immunoregulatory role in tumours. Here, we conducted a retrospective patient analysis to evaluate the effectiveness of PDT plus immune checkpoint inhibitors (ICIs) in gastric cancer. Further, we performed a dynamic analysis of gastric cancer patients receiving PDT to clarify its effects on anti-tumour immunity. METHODS: Forty ICI-treated patients that received PDT or not were retrospectively analysed. Five patients with gastric adenocarcinoma were enrolled for sample collection before and after PDT. Single-cell RNA/T cell receptor (TCR) sequencing, flow cytometry and histological exanimation were used to analyse the collected specimens. RESULTS: Patients in PDT group had a significantly better OS after ICI treatment than those in No PDT group. Single-cell analysis identified ten cell types in gastric cancer tissues and four sub-populations of T cells. Immune cell infiltration increased in the tumours after PDT and the circular immune cells showed consistent alterations. TCR analysis revealed a specific clonal expansion after PDT in cytotoxic T lymphocytes (CTL), but a constriction in Tregs. The B2M gene is upregulated in tumour cells after PDT and is associated with immune cell infiltration. Several pathways involving the positive regulation of immunity were enriched in tumour cells in the post-PDT group. The interactions following PDT were increased between tumour cells and effector cells but decreased between Tregs and other immune cells. Some co-stimulatory signaling emerged, whereas co-inhibitory signaling disappeared in intercellular communication after PDT. CONCLUSIONS: PDT elicits an anti-tumour response through various mechanisms and is promising as an adjuvant to enhance ICI benefit.

Water-Land-Food Nexus for Sustainable Agricultural Development in Main Grain-Producing Areas of North China Plain.

Stable and sustainable food production is an important guarantee for national security and social stability. The uneven distribution of cultivated land and water resources will threaten national food security. In this study, we adopt the Gini coefficient and water-land matching coefficient for exploring the water-land nexus in the main grain-producing areas of North China Plain (NCP) from 2000 to 2020. The water-land-food nexus considering grain crop production structure is further explored from spatial and temporal multi-scales. The results show the following: (1) The Gini coefficient presents an increasing trend in the NCP, indicating an increasing imbalance in the water-land matching degree among inter-regions. (2) There are significant differences in the WL nexus and WLF nexus among regions, showing a spatial pattern of "worse in the north and better in the south". (3) The cities which belonged to the low WL-low WLF and high WL-low WLF should be considered as key targets when formulating policies. (4) Adjusting the wheat-maize biannual system, optimizing the grain cultivation structure, promoting semi-dryland farming, and developing low water-consuming and high-yielding crop varieties are essential measures for these regions. The research results provide significant reference for the optimal management and sustainable agricultural development of agricultural land and water resources in NCP.

Photodynamic therapy in combination with immune checkpoint inhibitors plus chemotherapy for first-line treatment in advanced or metastatic gastric or gastroesophageal junction cancer: A phase 2-3 clinical trial protocol.

Introduction: The immune checkpoint inhibitor (ICI) has been approved as the first-line therapy for metastatic gastric cancer in China. The treatment response of immune checkpoint inhibitor is highly dependent on the immune condition within the tumor microenvironment. Photodynamic therapy (PDT) has a long history in cancer treatment, and recent studies showed it had an immunomodulatory effect on the tumor. Here we will conduct a trial to assess whether or not a combination with Photodynamic therapy will improve the outcomes of immune checkpoint inhibitor-based treatment in patients with advanced or metastatic gastric cancer. Methods: This study is a single-center, open-label, randomized controlled, phase 2-3 trial. Patients (18-65 years old) with untreated gastric or gastroesophageal junction adenocarcinoma will be eligible for this trial. Sixty participants will be enrolled and randomly divided into the test group (n = 30) and control group (n = 30) to receive photodynamic therapy in combination with immune checkpoint inhibitor plus chemotherapy and immune checkpoint inhibitor plus chemotherapy, respectively. The primary is progression-free survival (PFS). The secondary outcomes include objective response rates (ORRs) and the occurrence of adverse events. In addition, we will also assess the changes in peripheral blood mononuclear cells (PBMCs) and tumor microenvironment after photodynamic therapy treatment in the test group. Evaluation of the tumor response will be performed every two cycles for a maximum of eight cycles. Discussion: Photodynamic therapy has an immunomodulatory effect on the tumor microenvironment; however, this has not been demonstrated for gastric cancer in a clinical trial. Based on our experience of photodynamic therapy treatment in digestive tract tumors, we plan to conduct a randomized controlled trial on this topic. This will be the first study to evaluate the synergistic effect of photodynamic therapy with immunochemotherapy for patients with advanced gastric cancer. Ethics and dissemination: It was approved by the Institutional Research Ethics Committee of Lanzhou University Second Hospital (No. 2022A-491). When this trial is completed, it will be shared at conferences and submitted for a potential publication in a peer-reviewed journal. Clinical Trial Registration: http://www.chictr.org.cn/, identifier ChiCTR2200064280.

Case Report: Chemotherapy-free treatment with camrelizumab and anlotinib for elderly patients with KRAS and TP53 mutated advanced lung cancer.

Background: Lung cancer is a major public health issue and an enormous burden on society in China. Most lung cancers occur in elderly patients with non-small cell lung cancer (NSCLC), and many factors limit their treatment options. Chemotherapy-free therapy can avoid psychological fear, treatment pain, and adverse reactions caused by chemotherapy. Patients with non-small cell lung cancer with tumour protein p53 (TP53) gene mutations or Kirsten rat sarcoma viral oncogene homologue (KRAS) gene mutations tend to be more sensitive to anlotinib or programmed cell death protein 1 (PD-1) drugs. However, Kirsten rat sarcoma viral oncogene homologue is a proto-oncogene downstream of the epidermal growth factor receptor (EGFR) gene; therefore, if the Kirsten rat sarcoma viral oncogene homologue gene has an activating mutation, EGFR-targeted drug resistance may occur. Further studies are needed to explore whether patients with dual Kirsten rat sarcoma viral oncogene homologue and tumour protein p53 mutations can be treated with targeted immunotherapy without chemotherapy. Case presentation: A 74-year-old man was referred to the Lanzhou University Second Hospital due to chest tightness, shortness of breath, and weight loss for 2 months and was diagnosed with moderately to poorly differentiated adenocarcinoma. Laboratory examinations showed increased alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), cancer antigen (CA)-125, and CA199 levels, and gene sequencing indicated mutations in Kirsten rat sarcoma viral oncogene homologue and tumour protein p53. Immunohistochemical analysis showed positive PD-L1 and PD-1 expression. Peripheral blood immune checkpoint test using flow cytometry indicated that the PD-1 + CD8 levels were positive. After multi-disciplinary treatment, therapy with a combination of anlotinib and camrelizumab was initiated. Camrelizumab 200 mg was administered intravenously once every 3 weeks. Anlotinib 12 mg was administered orally daily before breakfast for 2 weeks with a week of rest in every cycle of 21 days. A reduction in alpha-fetoprotein, carcinoembryonic antigen, CA125, CA199, and CA724 levels was observed up to the first cycle, which decreased within the normal limits up to the second cycle and continued until the eighteenth cycle. The patient's chest tightness, shortness of breath, weight loss, and other symptoms significantly improved following treatment. Computed tomography imaging showed that the neoplastic lesion was dramatically reduced. The patient is currently being followed-up for more than 2 years to evaluate the duration of the response. Conclusion: Chemotherapy-free immunotherapy combined with targeted therapy is an effective treatment for advanced non-small cell lung cancer in elderly patients with Kirsten rat sarcoma viral oncogene homologue and tumour protein p53 mutations. Such therapies should be supported with further clinical studies with larger sample sizes.

Interaction between gut microbiota and tumour chemotherapy

Chemotherapeutic drugs play an important role in the treatment of cancer, but the individual differences of patients' sensitivity to chemotherapeutic drugs and the drug resistance of chemotherapeutic drugs have always been a thorny problem in clinical treatment. In recent years, with the progress in research on human microbiota, gut microbiome plays an increasingly important role in the diagnosis and treatment of diseases. Studies have shown that gut microbiota can regulate the tumour microenvironment and affect the efficacy and toxicity of chemotherapy through a variety of mechanisms. This paper focuses on the specific mechanism that gut microbiota uses to influence chemotherapy and the potential therapeutic effect of supplementing with probiotics, to provide an important basis for individualised treatment strategies to be used when treating malignant tumours (AU)

Radiomics-based prediction of response to immune checkpoint inhibitor treatment for solid cancers using computed tomography: a real-world study of two centers.

BACKGROUND: Immune checkpoint inhibitors (ICIs) represent an approved treatment for various cancers; however, only a small proportion of the population is responsive to such treatment. We aimed to develop and validate a plain CT-based tool for predicting the response to ICI treatment among cancer patients. METHODS: Data for patients with solid cancers treated with ICIs at two centers from October 2019 to October 2021 were randomly divided into training and validation sets. Radiomic features were extracted from pretreatment CT images of the tumor of interest. After feature selection, a radiomics signature was constructed based on the least absolute shrinkage and selection operator regression model, and the signature and clinical factors were incorporated into a radiomics nomogram. Model performance was evaluated using the training and validation sets. The Kaplan-Meier method was used to visualize associations with survival. RESULTS: Data for 122 and 30 patients were included in the training and validation sets, respectively. Both the radiomics signature (radscore) and nomogram exhibited good discrimination of response status, with areas under the curve (AUC) of 0.790 and 0.814 for the training set and 0.831 and 0.847 for the validation set, respectively. The calibration evaluation indicated goodness-of-fit for both models, while the decision curves indicated that clinical application was favorable. Both models were associated with the overall survival of patients in the validation set. CONCLUSIONS: We developed a radiomics model for early prediction of the response to ICI treatment. This model may aid in identifying the patients most likely to benefit from immunotherapy.

Difference in Intestinal Flora and Characteristics of Plasma Metabonomics in Pneumoconiosis Patients.

From the two perspectives of intestinal flora and plasma metabolomics, the mechanism of occurrence and development of pneumoconiosis was explored to provide a new target for the prevention and treatment of pneumoconiosis. In this study, 16S ribosome DNA (16SrDNA) gene sequencing technology was used to analyze the differences in intestinal flora of each research group through operational taxonomic units (OUT) analysis, cluster analysis, principal component analysis (PCA), partial least square discriminant analysis (PLS-DA), Kyoto Encyclopedia of Genes and Genomes (KEGG), and other analytical methods were used to analyze the differences in plasma metabolites between the study groups. Metabonomics analysis showed that the plasma metabolites of pneumoconiosis patients were significantly different from those of normal people. Fold change > 2; vip > 1; p < 0.05 were the screening criteria. In the positive and negative mode, we screened ten types of differential metabolites. These ten metabolites were upregulated to varying degrees in the pneumoconiosis patients. Seven metabolic pathways were obtained by analyzing the metabolic pathways of different metabolites. Among them, the aminoacyl tRNA biosynthesis pathway changed most obviously. The α diversity of two groups of intestinal flora was analyzed using the 16SrDNA technique. The results showed that there was no significant difference in ACE, Chao1, Shannon, or Simpson in the two groups (p > 0.05). Beta diversity analysis showed that there were differences in microbial communities. In pneumoconiosis patients, the abundance of Prevotellaceae increased, and the other nine species decreased. Compared to the control group, the abundance of Prevotellaceae in the intestinal flora of pneumoconiosis increased, and the abundance of the other nine species decreased. Compared to controls, ten substances in the plasma metabolites of pneumoconiosis patients were upregulated. Seven metabolic pathways were obtained by analyzing the metabolic pathways of different metabolites. Among them, the aminoacyl tRNA biosynthesis pathway changed most significantly. This provided a theoretical basis for further study on the pathogenesis, early prevention, and treatment of pneumoconiosis.

Interaction between gut microbiota and tumour chemotherapy.

Chemotherapeutic drugs play an important role in the treatment of cancer, but the individual differences of patients' sensitivity to chemotherapeutic drugs and the drug resistance of chemotherapeutic drugs have always been a thorny problem in clinical treatment. In recent years, with the progress in research on human microbiota, gut microbiome plays an increasingly important role in the diagnosis and treatment of diseases. Studies have shown that gut microbiota can regulate the tumour microenvironment and affect the efficacy and toxicity of chemotherapy through a variety of mechanisms. This paper focuses on the specific mechanism that gut microbiota uses to influence chemotherapy and the potential therapeutic effect of supplementing with probiotics, to provide an important basis for individualised treatment strategies to be used when treating malignant tumours.

RECIST 1.1 versus mRECIST for assessment of tumour response to molecular targeted therapies and disease outcomes in patients with hepatocellular carcinoma: a systematic review and meta-analysis.

OBJECTIVES: Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1) and modified RECIST (mRECIST) are commonly used to assess tumour response. Which one is better to evaluate efficacy after molecular targeted therapies in hepatocellular carcinoma (HCC) patients is still controversial. A systemic review was performed to compare the objective response rate (ORR) and disease control rate (DCR) and a meta-analysis was conducted to compare the correlation between objective response and overall survival (OS). DESIGN: Systematic review and meta-analysis using the Grading of Recommendations Assessment, Development and Evaluation approach. DATA SOURCES: EMBASE, PubMed, Web of Science and Cochrane Library were searched through 31 December 2021. ELIGIBILITY CRITERIA: We included studies assessing the efficacy of molecular targeted therapy for HCC according to both RECIST 1.1 and mRECIST. DATA EXTRACTION AND SYNTHESIS: Two investigators extracted data independently. The consistency between RECIST 1.1 vs mRECIST is measured by the k coefficient. HRs with corresponding 95% CIs were used for meta-analysis. RESULTS: 23 studies comprising 2574 patients were included in systematic review. The ORR according to mRECIST is higher than RECIST1.1 (15.9% vs 7.8%, p<0.001). The DCR is similar (68.4% vs 67.2%, p=0.5). The agreement of tumour response is moderate for objective response (k=0.499) and perfect for progressive disease (k=0.901), calculated from 8 studies including 372 patients. OS was significantly longer in response group than non-response group according to mRECIST (HR 0.56, 95% CI 0.41 to 0.78, p=0.0004) calculated from 7 studies including 566 patients, however, the RECIST1.1 could not distinguish the OS well (HR 0.68, 95% CI 0.44 to 1.05, p=0.08). Subgroup analusis by type of treatment was conducted. CONCLUSIONS: mRECIST may be more accurate than RECIST 1.1 in assessing ORR after molecular targeted therapies in HCC patients and can better assess the prognosis. However, the performance of both criteria in assessing disease progression is identical. PROSPERO REGISTRATION NUMBER: CRD42020200895. ETHICS APPROVAL: Ethics approval is not required in this meta-analysis.

BUB1 predicts poor prognosis and immune status in liver hepatocellular carcinoma.

Accurate assessment of the tumour immune microenvironment promotes individualized immunotherapy regimens and screens dominant populations suitable for immunotherapy. Therefore, potential molecular markers were investigated to make an overall assessment of the immune microenvironment status of liver hepatocellular carcinoma (LIHC). In this study, a total of 121 differentially expressed genes (DEGs) were identified, and DEGs were enriched in the epithelial-mesenchymal transition, hypoxia, myogenesis, and p53 pathways. A total of 20 hub genes were selected and a strong correlation was identified between these hub genes and prognosis. The expression of budding uninhibited by benzimidazoles 1 (BUB1) was found to be upregulated in LIHC and was strongly related to immune cells and immune checkpoint molecule expression. Immunohistochemistry (IHC) indicated that BUB1 expression was higher in LIHC tissues than in normal liver tissues. BUB1 knockdown resulted in reduced proliferation and vertical migration ability of LIHC cells, and reduced the expression of phospho-SMAD family member 2 and phospho-SMAD family member 3 proteins. IHC showed that BUB1 expression was accompanied by immune cell infiltration into LIHC tissues. These results suggest that BUB1 may serve as a potential prognostic biomarker for LIHC and as an indicator of its immune status.

Prognostic value of lymph node micrometastasis in esophageal cancer: A systematic review and meta-analysis.

Objective: Whether lymph node micrometastasis (LNM) increases the risk in esophageal cancer patients remains controversial. We conducted a systematic review and meta-analysis to explore the prognosis value of LNM in esophageal cancer patients. Methods: Two reviewers independently searched electronic databases, including PubMed, Embase, and the Cochrane Library, for eligible citations until February 2022. We calculated pooled estimates of the hazards ratio with a random-effects model. The certainty of evidence was determined by the Grade of Recommendations Assessment, Development, and Evaluation (GRADE) method. A sensitivity analysis was performed to assess the stability. Publication bias was assessed using funnel plots and Egger's test. We also performed subgroup analysis to explore the source of heterogeneity. Results: A total of 16 studies, with 1,652 patients, were included. The overall survival (OS) was significantly increased with LNM negativity compared with LNM positivity (HR 1.95; 95% CI, 1.53-2.49; P < 0.001; I2 = 0.0%, P = 0.930; certainty of evidence: low). Relapse-free survival (RFS) was significantly increased with LNM negativity compared with LNM positivity (HR 3.39; 95% CI, 1.87-6.16; P < 0.001; I2 = 50.18%, P = 0.060; certainty of evidence: moderate). No significant difference was observed in recurrence between the two groups (certainty of evidence: low). Sensitivity analysis revealed a stable trend. In addition, the funnel plot and Egger's test did not show significant publication bias. Conclusion: LNM positivity worsens the prognosis in esophageal cancer, and the evidence for RFS is moderate. Future relevant high-quality studies are warranted to validate our results further and provide a reference for guidelines. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier (CRD42022321768).

Prognostic value of FOXP3+ regulatory T cells in patients with diffuse large B-cell lymphoma: a systematic review and meta-analysis.

OBJECTIVES: We aimed to comprehensively evaluate the relationship between forkhead box P3 (FOXP3+) regulatory T cell (Treg) expression and diffuse large B-cell lymphoma (DLBCL) prognosis and to explore the sources of heterogeneity of the results. DESIGN: Systematic review and meta-analysis. DATA SOURCES: We searched the Cochrane Library, PubMed, Embase and Web of Science databases up to 5 December 2021. ELIGIBILITY CRITERIA: We included studies that analysed the prognostic significance of FOXP3+ Tregs in DLBCL. We included studies reported in Chinese or English that reported HRs and related 95% CIs for prognosis. DATA EXTRACTION AND SYNTHESIS: We extracted data from eligible studies. HRs and 95% CIs were used to assess the prognostic value. RESULTS: Fourteen eligible studies were identified. FOXP3+ Treg expression was not associated with overall survival (OS) (HR=0.72, 95% CI 0.45 to 1.16) or progression-free survival (HR=0.86, 95% CI 0.54 to 1.38). The three approaches used to measure FOXP3+ Treg expression (pinteraction<0.001) may be the source of the heterogeneity of the results. Subgroup analysis found that a higher expression of FOXP3+ Tregs was associated with better OS in all populations and in Asians when FOXP3+ Treg expression was measured by the number of positive cells (HR=0.36 (95% CI 0.22 to 0.58) in the former, HR=0.33 (95% CI 0.20 to 0.55) in the latter) or the percentage of positive cells (HR=0.49 (95% CI 0.27 to 0.89) in the former, HR=0.38 (95% CI 0.21 to 0.70) in the latter). However, when measured by the score, inverse results were found (HR=1.56, 95% CI 1.01 to 2.42). CONCLUSIONS: Approaches to measuring FOXP3+ Treg expression might be the major source of heterogeneity in studies of the prognostic significance of FOXP3+ Tregs in DLBCL. FOXP3+ Treg expression might be used to predict the prognosis of patients with DLBCL when FOXP3+ Treg expression is calculated by the number or the percentage of positive cells, especially in Asian populations.

Bibliometric Analysis and Systematic Review of Global Coronavirus Research Trends Before COVID-19: Prospects and Implications for COVID-19 Research.

Coronaviruses (CoV) cause respiratory and intestinal infections. We conducted this bibliometric analysis and systematical review to explore the CoV-related research trends from before COVID-19. We systematically searched the Ovid MEDLINE, Ovid Embase, and Web of Science (WOS) databases for published bibliometric analyses of CoV from database inception to January 24, 2021. The WOS Collection was searched from inception to January 31, 2020, to acquire the CoV-related publications before COVID-19. One-Way ANOVA and Bonferroni multiple-comparison tests were used to compare differences. Visualization mapping and keyword cluster graphs were made to illustrate the research topics and hotpots. We included 14,141 CoV-related publications for the bibliometric analysis and 16 (12 articles) CoV-related bibliometric analyses for the systematic review. Both the systematic review and bibliometric analysis showed (1) the number of publications showed two steep upward trajectories in 2003-2004 and in 2012-2014; (2) the research hotpots mainly focused on the mechanism, pathology, epidemiology, clinical diagnosis, and treatment of the coronavirus in MERS-CoV and SARS-Cov; (3) the USA, and China; the University of Hong Kong; and Yuen KY, came from the University of Hong Kong contributed most; (4) the Journal of Virology had the largest number of CoV related studies. More studies should focus on prevention, diagnosis, and treatment in the future.