Association between inflammatory factors and melanoma: a bidirectional Mendelian randomization study.

PURPOSE: This study performed a bidirectional Mendelian randomization (MR) analysis to elucidate the causal relationships of C-reactive protein and 41 inflammatory regulators with melanoma, including data from UK Biobank, Cardiovascular Risk in Young Finns Study, and Cohorts for Inflammation Work Group. METHODS: We selected the inverse variance weighting (IVW) to merge the estimated causal effects of multiple SNPs into a weighted average. To evaluate the heterogeneities of IVW, the Cochran Q statistic, and I2 index were used. What's more, several sensitivity analyses were employed, including IVW, MR-Egger, weighted median, and Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO). RESULTS: With SNPs reaching P < 5 × 10-8, the analyses findings revealed that IL-16 had a significant positively association with genetically risk of melanoma (ORIVW: 1.05; 95% CI: 1.03-1.07; P < 0.001), and high levels of MCP1 (ORIVW: 1.13; 95% CI: 1.03-1.23; P = 0.01) were suggestively associated with melanoma susceptibility. What's more, TNF-ß (ORIVW: 1.07; 95% CI: 1.01-1.13; P = 0.02) and IL-8 (ORIVW: 1.08, 95% CI: 1.01-1.16; P = 0.03) were demonstrated a positive association with the risk of melanoma under a less stringent cut-off (P < 5 × 10-6). Conversely, we found a facilitative effect of melanoma susceptibility on IP-10 and inhibitory effects on IL-6, IL-1b, and GRO-α. CONCLUSION: The genetic evidence that we have uncovered indicates a potential association between the levels of specific inflammatory markers (IL-16, IL-8, MCP-1, and TNF-ß) and the risk of melanoma. Further research is imperative to translate these findings into clinical applications.

Association of ankylosing spondylitis with the risk of cancer: a meta- analysis of cohort studies.

OBJECTIVES: The potential impact of ankylosing spondylitis (AS) on cancer risk remains unclear. This study seeks to investigate the relationship between AS and different types of cancers. METHODS: A literature search of the PubMed, Embase and Cochrane Library up to July 10th, 2023, was conducted. Two investigators selected eligible studies and extracted relevant data. The study used the random-effects model to explore the causality between AS and cancer, utilising relative risk (RR) as a measure for the study. RESULTS: A total of 20 cohorts with >330 000 participants were included. The pooling analysis shows AS being associated with a higher risk of cancers (RR = 1.16, 95% CI : 1.07-1.26, p= 0.001, I2=70.60%). In the subgroup analysis, AS has a higher cancer risk in Asia, but this association is not significant in Europe. Individual investigations indicate that AS is associated with an increased risk of bone cancer (RR = 3.41, 95% CI : 1.45-7.99, p= 0.005, I2=0.00%), thyroid gland cancer (RR = 1.76, 95% CI : 1.29-2.40, p< 0.001, I2=13.70%), multiple myeloma (RR = 1.74, 95% CI : 1.42-2.15, p< 0.001, I2=27.20%), leukaemia (RR = 1.52, 95% CI : 1.27-1.82, p< 0.001, I2=0.00%), kidney cancer (RR = 1.45, 95% CI : 1.08-1.94, p= 0.014, I2=0.00%), prostate cancer (RR = 1.43, 95% CI : 1.17-1.74, p< 0.001, I2=82.80%), and non-Hodgkin's lymphoma (RR = 1.42, 95% CI : 1.17-1.73, p< 0.001, I2=0.00%). However, there is no significant correlation with connective tissue cancer, brain cancer, testicular and other male cancers, bladder cancer, female cancers, skin cancer, and cancers of the digestive system and respiratory system. CONCLUSION: AS appears to be related to cancer development. The results highlighted the necessity for large-scale studies, considering influencing factors such as AS course, medication histories, and potential biases when examining cancer risk.

Transcription factor POU4F2 promotes colorectal cancer cell migration and invasion through hedgehog-mediated epithelial-mesenchymal transition.

As a POU homeodomain transcription factor, POU4F2 has been implicated in regulating tumorigenic processes in various cancers. However, the role of POU4F2 in colorectal cancer (CRC) remains unclear. Here, we revealed that POU4F2 functions as a tumor promotor in CRC. Bioinformatics analysis in specimens from CRC patients and expression analysis in CRC cell lines showed that POU4F2 was upregulated at the mRNA and protein levels in CRC. Depletion of POU4F2 suppressed the metastatic phenotypes of CRC cells, including cell migration, invasion, and the expression of epithelial-mesenchymal transition (EMT) markers. Moreover, depletion of POU4F2 decreased the number of lung metastatic nodes in nude mice. Mechanistically, POU4F2 positively regulated the Hedgehog signaling pathway, as inferred from the downregulation of the expression of sonic Hedgehog homolog, patched 1, Smoothened, and GLI family zinc finger 1 in vitro and vivo following silencing of POU4F2. Furthermore, the SMO agonist SAG reversed the effects of POU4F2 knockdown in CRC. Functionally, POU4F2 contributed to the Hedgehog signaling-regulated activation of the EMT process and promotion of CRC cell migration and invasion. Collectively, these findings elucidated the role of POU4F2 as a tumor promotor in CRC through the regulation of Hedgehog signaling-mediated EMT and suggested that POU4F2 suppression might be a promising therapeutic target in inhibiting CRC metastasis.

Successful treatment of multidrug-resistant Acinetobacter baumannii meningitis with ampicillin sulbactam in primary hospital.

Introduction: Acinetobacter baumannii nosocomial infections, especially those due to multi-drug resistant strains, are increasingly detected. We want to find the effective treatment measures about multi-resistant Acinetobacter baumannii infections through this research.Methodology: The clinical features and the outcomes of twelve cases of nosocomial Acinetobacter baumannii meningitis treated with ampicillin sulbactam and intrathecal use of amikacin are reported in primary hospital. All the patients had fever, neck stiffness or meningeal signs, and a low consciousness level, and in their cerebrospinal fluid (CSF), pleocytosis, a low glucose level, and an elevated protein level were noted. For all CSF isolates were resistant to at least two antibiotics used in empirical therapy (third and fourth generation cephalosporins, carbapenems or piperacillin/tazobactam). Four cases sputum culture prompted the growth of Acinetobacter baumannii. Two CSF isolates were intermediate resistant to ampicillin sulbactam, only sensitive to amikacin. The two patients were treated with ampicillin sulbactam and intrathecal use of amikacin.Results: The dosages and the duration of treatment with ampicillin sulbactam were 2 g/1 g every 6 hours and 9-21days. Eleven patients were cured and one patient died of meningitis (8.3%). This patient died of severe respiratory Acinetobacter baumannii infection and severe sepsis. One patient had mild nausea and discomfort, given metoclopramide therapy. There were no serious side effects with the ampicillin sulbactam treatment.Conclusions: In conclusion, ampicillin sulbactam may be effective as therapy for meningitis caused by Acinetobacter baumannii resistant to imipenem and other ß-lactam drugs. Meanwhile, continuous lumbar external drainage and intermittent intrathecal use of amikacin were necessary methods.

Association between human blood metabolome and the risk of gastrointestinal tumors.

BACKGROUND: The prevalence of gastrointestinal tumors continues to be significant. To uncover promising therapeutic targets for these tumors, we rigorously executed a Mendelian randomization (MR) study to comprehensively screen the blood metabolomes for potential causal mediators of five frequently encountered gastrointestinal tumors (Liver Cancer, Colorectal Cancer, Esophageal Cancer, Gastric Cancer and Pancreatic Cancer). METHODS: We selected a comprehensive set of 137 distinct blood metabolites derived from three large-scale genome-wide association studies (GWASs) involving a total of 147827 participants of European ancestry. The gastrointestinal tumors-related data were obtained from a GWAS conducted within the Finnish study. Through meticulous MR analyses, we thoroughly assessed the associations between blood metabolites and gastrointestinal tumors. Additionally, a phenome-wide MR (Phe-MR) analysis was employed to investigate the potential on-target side effects of metabolite interventions. RESULTS: We have identified 1 blood metabolites, namely isovalerylcarnitine (ORlog10: 1.01; 95%CI, 1.01-1.02; P = 1.81×10-7), as the potential causal mediators for liver cancer. However, no potential pathogenic mediators were detected for the other four tumors. CONCLUSIONS: The current systematic MR analysis elucidated the potential role of isovalerylcarnitine as a causal mediator in the development of liver cancer. Leveraging the power of Phe-MR study facilitated the identification of potential adverse effects associated with drug targets for liver cancer prevention. Considering the weighing of pros and cons, isovalerylcarnitine emerges as a promising candidate for targeted drug interventions in the realm of liver cancer prevention.

Prognostic value of preoperative circulating tumor DNA in non-small cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: Several recent studies have reported the increasing application of preoperative circulating tumor DNA (ctDNA) as a biomarker of tumor burden for guiding potential postoperative treatment strategies. METHODS: A meta-analysis of prospective/retrospective cohort studies was conducted to compare the prognosis of preoperatively genetically positive and genetically negative NSCLC patients. The endpoints used in the included studies were overall survival (OS) and recurrence-free survival (RFS). The objective of the meta-analysis was to comprehensively explore the prognostic value of preoperative ctDNA for patients with non-small-cell lung cancer (NSCLC) and its significance in guiding postoperative adjuvant therapy (AT) in patients with NSCLC. RESULTS: The preliminary analysis identified 1565 studies, among which only 11 studies fulfilled the eligibility criteria and were finally included in the present systematic review and meta-analysis. The statistical results revealed that the expression of preoperative ctDNA was associated with worse RFS (HR = 3.00; 95% CI 2.26-3.98; I2 = 0%) and OS (HR = 2.77; 95% CI 1.67-4.58; I2 = 0%), particularly in lung adenocarcinoma (LUAD) patients (RFS: HR = 3.46; 95% CI 2.37-5.05; I2 = 0%; OS: HR = 3.52; 95% CI 1.91-6.49; I2 = 0%) and patients with I-II stage of NSCLC (RFS: HR = 2.84; 95% CI 1.88-4.29; I2 = 0%; OS: HR = 2.60; 95% CI 1.43-4.74; I2 = 0%). Moreover, compared to patients with negative preoperative ctDNA, patients with positive preoperative ctDNA presented greater survival benefits (HR = 0.39; 95% CI 0.22-0.67; I2 = 2%) from postoperative AT. CONCLUSION: The evaluation of the prognostic value of preoperative ctDNA revealed that preoperative ctDNA might be used as a prognostic biomarker for patients with LUAD or those with stage I-II NSCLC. In addition, postoperative AT is recommended for NSCLC patients with positive preoperative ctDNA, regardless of the disease stage and subtype.

Hedgehog pathway and cancer: A new area (Review).

In years of research on classical pathways, the composition, information transmission mechanism, crosstalk with other pathways, and physiological and pathological effects of hedgehog (HH) pathway have been gradually clarified. HH also plays a critical role in tumor formation and development. According to the update of interpretation of tumor phenotypes, the latest relevant studies have been sorted out, to explore the specific mechanism of HH pathway in regulating different tumor phenotypes through gene mutation and signal regulation. The drugs and natural ingredients involved in regulating HH pathway were also reviewed; five approved drugs and drugs under research exert efficacy by blocking HH pathway, and at least 22 natural components have potential to treat tumors by HH pathway. Nevertheless, there is a deficiency of existing studies. The present review confirmed the great potential of HH pathway in future cancer treatment with factual basis.

Intervention of epithelial mesenchymal transition against colon cancer cell growth and metastasis based on SOX21/POU4F2/Hedgehog signaling axis.

AIMS: Colon cancer poses a major threat to human health and a heavy burden on the national economy. As a member of the SOX transcription factor family, SRY-box transcription factor 21 (SOX21) is associated with various cancers, but its mechanism of action in colon cancer remains unclear. This study focused on the molecular mechanisms of transcription factor SOX21 in proliferation and metastasis of colon cancer cells. MAIN METHODS: We analyzed SOX21 expression level and its impact on survival in colon cancer patients by bioinformatics analysis. We used public databases for gene correlation, GSEA enrichment analysis. Cell function experiments (colony formation assay, wound healing assay, Transwell migration and invasion assay) were utilized to determine the impact of SOX21 silencing and over-expression on cell proliferation and metastasis. The luciferase reporter assay, CUT&RUN-qPCR assay and Methylation Specific PCR were used to explore SOX21-POU class 4 homeobox 2 (POU4F2) molecular interactions. The molecular mechanisms were verified by Quantitative real-time PCR and Western blot analysis. KEY FINDINGS: SOX21 is highly expressed and affects the overall survival of colon cancer patients. SOX21 can attenuates POU4F2 methylation state by binding with it. In addition, this interaction facilitate its transcriptional activation of Hedgehog pathway, mediates epithelial-mesenchymal transition (EMT), consequently promoting the proliferation and metastasis of colon cancer cells. SIGNIFICANCE: Our study reveals that SOX21 is an oncogenic molecule and suggests its regulatory role in colon carcinogenesis and progression, providing new insights into the treatment of this disease.

Integrated Bioinformatics and Experimental Analysis of Long Noncoding RNA Associated-ceRNA as Prognostic Biomarkers in Advanced Stomach Adenocarcinoma.

BACKGROUND: Advanced stomach adenocarcinoma (ASTAD) is a highly malignant and prognostically poor stage of gastric cancer. Recently, long noncoding RNA (lncRNA) was found to play a crucial role, including as competing endogenous RNA (ceRNA) in cancer. However, studies on large-scale sample in ASTAD are still lacking, thus we constructed the ceRNA network of ASTAD to explore its molecular mechanism. METHODS: We compared the expression of mRNAs, lncRNAs and miRNAs between ASTAD and normal tissues utilizing RNA-Seq and miRNA-seq Data from The Cancer Genome Atlas (TCGA). GO and KEGG enrichment analysis were executed for annotating the functions of differentially expressed mRNAs. Subsequently, we investigated the expression correlations between the differentially expressed lncRNAs and their respective mRNAs by constructing a ceRNA network. Kaplan-Meier survival analysis was used to assess the relationship between high/low risk scores based on this network with patient prognosis in TCGA training cohort and GSE15459 validation cohort. In vitro functional assays were employed to verify the cancer-promoting effects of key lncRNAs in the ceRNA network and their possible mechanisms. RESULTS: In ASTAD tissues, a total of 176 lncRNAs, 124 miRNAs, and 2205 mRNAs were identified as differentially expressed. Our constructed ceRNA network consisted 6 differentially expressed lncRNAs (PVT1, MAGI2-AS3, KCNQ1OT1, LINC02086, AC125807.2 and LINC02535), 25 miRNAs and 130 mRNAs, and the risk score derived from these lincRNAs could predict ASTAD patient outcomes. Key lncRNA LINC02086 was experimentally verified to enhance proliferation and migration of gastric cancer cells by competitively binding to miR-93a-5p with MMP3. CONCLUSION: Our comprehensive ceRNA network for ASTAD provides valuable insights into its molecular mechanisms, and LINC02086 may be used as an innovative target for clinical treatment.

Review on chronic metabolic diseases surrounding bile acids and gut microbiota: What we have explored so far.

Bile acid, the final product of cholesterol breakdown, functions as a complex regulator and signaling factor in human metabolism. Chronic metabolic diseases pose significant medical challenges. Growing research underscores bile acids' capacity to enhance metabolism via diverse pathways, regulating disorders and offering treatment potential. Numerous bile-acid-triggered pathways have become treatment targets. This review outlines bile acid synthesis, its role as a signal in chronic metabolic diseases, and highlights its interaction with gut microbiota in different metabolic conditions. Exploring host-bacteria-bile acid links emerges as a valuable future research direction with clinical implications.

Resveratrol restrains colorectal cancer metastasis by regulating miR-125b-5p/TRAF6 signaling axis.

Colorectal cancer is one of the most common malignancies with a high incidence, metastatic tendency and low 5-year survival rate. Resveratrol, a polyphenolic compound has been shown to inhibit colorectal cancer metastasis in recent studies. Its underlying molecular mechanism remains to be elucidated. Our findings demonstrated that miR-125b-5p, acting as a tumor suppressor, was conspicuously down-regulated in both colorectal cancer tissues and cell lines. The expression of miR-125b-5p negatively correlated with the expression of its direct target TNF receptor associated factor 6 (TRAF6). Both miR-125b-5p overexpression and TRAF6 knockdown inhibited metastasis of colorectal cancer cells. In addition, we uncovered that resveratrol up-regulated miR-125b-5p by increasing its stability and suppressed TRAF6-induced signal pathway in a dose/time-dependent manner. Resveratrol could significantly curtail the migration and invasion of colorectal cancer cells, which was counteracted by miR-125b-5p knockdown or TRAF6 overexpression. These results indicated that resveratrol could restrain colorectal cancer metastasis by promoting miR-125b-5p/TRAF6 signaling axis. Furthermore, lung metastasis models of colorectal cancer were constructed by tail vein injection. Down-regulation of miR-125b-5p could facilitate colorectal cancer metastasis in vivo, which could be impeded by resveratrol. In conclusion, our findings delineated the miR-125b-5p/TRAF6 signaling axis as a novel molecular mechanism underlying the metastatic process in colorectal cancer, as well as a prospective therapeutic target. Resveratrol disrupts colorectal cancer metastasis by activating miR-125b-5p/TRAF6 signal pathway and might improve the clinical outcome of colorectal cancer patients with low expression of miR-125b-5p.

Clinical prognostic value of OSGIN2 in gastric cancer and its proliferative effect in vitro.

This study explored the promoting effect of oxidative stress-induced growth inhibitor family member 2(OSGIN2) on gastric cancer (GC) through public databases and in vitro experiments. The potential relationship between OSGIN2 expression, prognosis, functional enrichment of associated differential genes, immune infiltration, and mutational information in gastric cancer were comprehensively investigated using bioinformatics analysis. OSGIN2 was knocked down using small interfering RNA (siRNA) transfection for subsequent cell function testing. The results showed that gastric carcinoma cells and tissues contained high levels of OSGIN2, which was associated with a poor prognosis for GC patients. It was important in the cell cycle, autophagy, etc., and was related to a variety of tumor-related signal pathways. Knockdown of OSGIN2 inhibited tumor cell proliferation and contributed to cell cycle arrest. It was also correlated with tumor immune infiltrating cells (TILs), affecting antitumor immune function. Our analysis highlights that OSING2, as a new biomarker, has diagnostic and prognostic value in gastric cancer and is a potentially effective target in GC treatment.

Comprehensive bioinformatics and experimental analysis of SH3PXD2B reveals its carcinogenic effect in gastric carcinoma.

AIMS: We aim to explore the possibility and mechanism of SH3PXD2B as a reliable biomarker for gastric cancer (GC). MAIN METHODS: We used public databases to analyze the molecular characteristics and disease associations of SH3PXD2B, and KM database for prognostic analysis. The TCGA gastric cancer dataset was used for single gene correlation, differential expression, functional enrichment and immunoinfiltration analysis. SH3PXD2B protein interaction network was constructed by the STRING database. And the GSCALite database was used to explore sensitive drugs and perform SH3PXD2B molecular docking. The impact of SH3PXD2B silencing and over-expression by lentivirus transduction on the proliferation and invasion of human GC HGC-27 and NUGC-3 cells was determined. KEY FINDINGS: The high expression of SH3PXD2B in gastric cancer was related to the poor prognosis of patients. It may affect the progression of gastric cancer by forming a regulatory network with FBN1, ADAM15 and other molecules, and the mechanism may involve regulating the infiltration of Treg, TAM and other immunosuppressive cells. The cytofunctional experiments verified that it significantly promoted the proliferation and migration of gastric cancer cells. In addition, we found that some drugs were sensitive to the expression of SH3PXD2B such as sotrastaurin, BHG712 and sirolimus, and they had strong molecular combination of SH3PXD2B, which may provide guidance for the treatment of gastric cancer. SIGNIFICANCE: Our study strongly suggests that SH3PXD2B is a carcinogenic molecule that can be used as a biomarker for GC detection, prognosis, treatment design, and follow-up.

Inhibition of protein kinase C signal reduces ET receptor expression and basilar vasospasm after subarachnoid hemorrhage in rats.

Endothelin-1 (ET-1), acting through specific ET(A) and/or ET(B) receptors, plays an important role in cerebral vasospasm after subarachnoid hemorrhage (SAH). However, the mechanism remains unclear. In the present study, ET receptors' expression in the basiliar artery during cerebral vasospasm and the possible involvement of protein kinase C (PKC) were investigated using immunofluorescence staining and reverse transcriptase polymerase chain reaction (RT-PCR) in a rat SAH model of delayed cerebral vasospasm (DCVS). The cross-sectional area of the basilar artery in the SAH model group decreased in 2-3 days, and then gradually returned to normal. ET(A) receptor expression in endothelial cells of the basilar artery increased in day 2 after SAH, peaked at day 3 and remained increased till day 14. ET(B) receptor expression increased significantly in endothelial cells at day 3, peaked at day 7 and remained until day 14. RT-PCR result also revealed increased expressions of similar trends, but the expression of ET(B) receptor mRNA level tended to increase earlier than the protein level. When PKC inhibitor (RO-31-7549, 10(-6) mol/L, 50 µl) was administered 1, 6, 24, 32, 48 and 70 hours before cisternal injection, the expressions of the two ET receptors after day 3 decreased to varying degrees, while the vascular cross-sectional area was significantly higher (P < 0.05). The results suggest that the ET(A)/ET(B) receptors play an important role in cerebral vasospasm after SAH. Application of RO-31-7549 reduced the expression of ET receptors and reduced cerebral vasospasm, suggesting that inhibition of PKC signaling pathway could effectively reduce DCVS after SAH.

Exploring the Pharmacological Mechanism of the Effective Chinese Medicines Against Gynecological Cancer Based on Meta-Analysis Combined With Network Pharmacology Analysis.

This meta-analysis plus network pharmacology aimed to investigate whether traditional Chinese medicine (TCM) combined with chemotherapy is associated with more beneficial efficacy data in the treatment of gynecological cancer (GC). A total of 11 randomized controlled trials (RCTs) consisting of 863 GC patients were included. Results showed a better ORR (RR: 1.42, 95% CI: 1.18-1.71; I 2 = 21.4%; p = 0.282), DCR (RR: 1.13, 95% CI: 1.03-1.25; I 2 = 0.0%; p = 0.492), PD (RR: 0.27, 95% CI: 0.11-0.65, p = 0.003; I 2 = 0.0%, p = 0.930), and QOL (SMD: 0.85, 95% CI: 0.38-1.33, p = 0.005) and higher proportions of CD3+ T (WMD: 5.65, 95% CI: 4.23-7.08, p = 0.000; I 2 = 68.3%, p = 0.004), CD4+ T (WMD: 6.97, 95% CI: 5.35-8.59, p = 0.000; I 2 = 83.4%, p = 0.000), and the CD4+/CD8+ T ratio (WMD: 0.32, 95% CI: 0.23-0.42, p = 0.000; I 2 = 78.0%, p = 0.000). The number of adverse events (AEs) was significantly lower in the TCM + chemotherapy group. The active components and targets of 19 high-frequency Chinese medicines obtained from the meta-analysis were screened and explored in network pharmacology analysis. Also, a regulatory network of active components and targets, a core network and key genes, a diagram of protein interaction, network topology analysis, and gene body GO function and KEGG pathway enrichment analysis were performed. A total of 120 active components were identified. NPM1 and HSPA8 are the most critical target proteins in the core network of protein interaction. HSP90AA1 is the most important target protein in the TCM group. KEGG enrichment analysis showed that it was highly significant in the lipid and atherosclerotic pathways. Therefore, moderate evidence revealed that TCM plus chemotherapy has obvious advantages over chemotherapy alone in terms of tumor responses, QOL, peripheral blood lymphocyte levels, and fewer AEs in the treatment of GC. The potential important targets and core genes were displayed. Systematic Review Registration: www.crd.york.ac.uk/PROSPERO/, identifier CRD42021252500.

Association Between Metabolic Syndrome and Risk of Renal Cell Cancer: A Meta-Analysis.

Background: Metabolic syndrome (MetS) has been related to increased risks of a variety of cancers. However, the association between MetS and the risk of renal cell cancer (RCC) remains not fully determined. This meta-analysis was conducted to investigate whether MetS is independently associated with the risk of RCC in adults. Methods: Relevant observational studies were obtained by searching PubMed, Embase, Cochrane's Library, and Web of Science databases. Study characteristics and outcome data were extracted independently by two authors. The random-effect model was used for meta-analysis considering the possible influence of between-study heterogeneity. Predefined subgroup analyses were used to evaluate the possible influences of study characteristics on the outcome. Results: Eight studies involving 10,601,006 participants contributed to the meta-analysis. Results showed that MetS was independently associated with a higher risk of RCC in adult population (risk ratio [RR]: 1.62, 95% confidence interval [CI]: 1.41 to 1.87, p<0.001; I2 = 85%). Subgroup analyses showed consistent association in men (RR: 1.52, 95% CI: 1.23 to 1.89, p<0.001) and in women (RR: 1.71, 95% CI: 1.28 to 2.27, p<0.001), in Asians (RR: 1.51, 95% CI: 1.25 to 1.83, p<0.001) and in Caucasians (RR: 1.76, 95% CI: 1.46 to 2.12, p<0.001), and in community derived (RR: 1.56, 95% CI: 1.34 to 1.82, p<0.001) and non-community derived population (RR: 1.87, 95% CI: 1.71 to 2.04, p<0.001). Differences in study design or quality score also did not significantly affect the association (p for subgroup difference both >0.05). Conclusions: MetS may be independently associated with RCC in adult population.

The difference of human gut microbiome in colorectal cancer with and without metastases.

Metastasis of colorectal cancer is deemed to be closely related to the changes in the human gut microbiome. The purpose of our study is to distinguish the differences in gut microbiota between colorectal cancer with and without metastases. Firstly, this study recruited colorectal cancer patients who met the established inclusion and exclusion criteria in the Oncology Department of Zhejiang Hospital of Traditional Chinese Medicine from February 2019 to June 2019. Fresh stool samples from healthy volunteers, non-metastatic patients, and metastatic patients were collected for 16S rRNA gene sequencing, to analyze the diversity and abundance of intestinal microorganisms in each group. The results showed that the microbial composition of the control group was more aplenty than the experimental group, while the difference also happened in the Tumor and the metastases group. At the phylum level, the abundance of Bacteroidetes significantly declined in the Tumor and the metastases group, compared with the control group. At the class level, Bacilli increased in experimental groups, while its abundance in the Tumor group was significantly higher than that in the metastases group. At the order level, the Tumor group had the highest abundance of Lactobacillales, followed by the metastases group and the control group had the lowest abundance. Overall, our study showed that the composition of the flora changed with the occurrence of metastasis in colorectal cancer. Therefore, the analysis of gut microbiota can serve as a supplement biological basis for the diagnosis and treatment of metastatic colorectal cancer which may offer the potential to develop non-invasive diagnostic tests.

What Causes Death in Esophageal Cancer Patients Other Than the Cancer Itself: A Large Population-Based Analysis.

Background: Researches on noncancer causes of death in patients with esophageal cancer (EC) are not in-depth. The objective of this paper is to broadly and deeply explore the causes of death in patients with EC, especially noncancer causes. Methods: Information about the demographics, tumor-related characteristics, and causes of death of patients with EC who met the inclusion criteria were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Calculated standardized mortality ratio (SMR) for all causes of death at different follow-up times and performed subgroup analyses. Results: In total, 63,560 patients with EC were retrieved from the public database. And 52,503 died during the follow-up period. Most deaths were due to EC itself within 5 years after diagnosis, but over 10 years, 59% EC patients died from noncancer causes. Cardiovascular disease was the major noncancer cause of death in patients with EC, accounting for 43%. Suicide and self-injury (2%) of EC patients should not be ignored. During the 1-year follow-up period, patients with EC had statistically highest risk of death from septicemia (SMR: 7.61; 95% CI: 6.38-9.00). Within more than 10 years after EC diagnosis, more and more patients died from chronic obstructive pulmonary disease (SMR: 2.38; 95% CI: 1.79-3.10). Conclusions: Although most patients with EC still died from the cancer itself, the role of noncancer causes of death should not be underestimated. These prompt clinicians to pay more attention to the risk of death caused by these noncancer causes, which can provide relevant measures in advance to intervene.

Is antibody-drug conjugate a rising star for clinical treatment of solid tumors? A systematic review and meta-analysis.

Antibody-drug conjugates (ADCs) show significant advantages in cancer treatment due to their high selectivity and anti-tumor activity, but the efficacy and safety of the treatment of solid tumors are unknown. We searched research databases, major conference proceedings and trial registries for randomized controlled trials (RCTs). Then, we selected qualified studies and extracted dates. Studies were assessed for quality, and a meta-analysis was conducted to quantify effects of ADCs on overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and adverse events (AEs). The within-study heterogeneity was evaluated by subgroup and sensitivity analysis. Eleven RCTs with 4353 participants were included. ADCs had better PFS (HR: 0.69, 95 % CI: 0.56-0.82) and OS (HR: 0.76, 95 % CI: 0.61-0.92). ADCs resulted in lower risk of febrile neutropenia in blood system. Conversely, ADC therapy had not a prepotent on ORR (RR: 1.36, 95 % CI: 0.71-2.60).