Tumor microenvironment responsive chitosan-coated W-doped MoOx biodegradable composite nanomaterials for photothermal/chemodynamic synergistic therapy.

Chemodynamic therapy (CDT), an approach that eradicates tumor cells through the catalysis of hydrogen peroxide (H2O2) into highly toxic hydroxyl radicals (·OH), possesses distinct advantages in tumor specificity and minimal side effects. However, CDT's therapeutic efficacy is currently hampered by the low production efficiency of ·OH. To address this limitation, this study introduces a water-soluble chitosan-coated W-doped MoOx (WMoOx/CS) designed for the combined application of photothermal therapy (PTT) combined with CDT. The W-doped MoOx (WMoOx) was synthesized in one step by the hydrothermal method, and its surface was modified by water-soluble chitosan (carboxylated chitosan, CS) to enhance its biocompatibility. WMoOx boasts a high near-infrared photothermal conversion efficiency of 52.66 %, efficiently transducing near-infrared radiation into heat. Moreover, the Mo4+/Mo5+ and W5+ ions in WMoOx catalyze H2O2 to produce ·OH for CDT, and the Mo5+/Mo6+ and W6+ ions in WMoOx reduce intracellular glutathione levels and prevent the scavenging of ·OH by glutathione. Crucially, the combination of WMoOx/CS and near-infrared light irradiation demonstrates promising synergistic antitumor effects in both in vitro and in vivo models, highlighting its potential for the combined application of PTT and CDT.

Association of Sleep Duration with Risk of All-Cause and Cause-Specific Mortality Among American Adults: A Population-Based Cohort Study.

Objective: To examine potential factors affecting sleep duration and explore its association with the risk of mortality among adults in the United States. Methods: The study population consisted of adults aged 26 to 79 years who participated in the National Health and Nutrition Examination Survey (NHANES) conducted from 2007 to 2016. Sleep duration was classified into three categories: short (<7 hours), optimal (7-8 hours), and long (≥9 hours). The associations between sleep duration and both all-cause mortality and cause-specific mortality (including heart disease, tumors, cerebrovascular disease, and others) were examined in the overall population and subgroups using weighted Cox regression models. Dose-response associations between sleep duration and risk of all-cause mortality were explored using restricted cubic spline (RCS) analyses. Additionally, a multinomial logistic regression analysis was conducted to investigate potential factors that influence sleep duration in adults. Results: The study included a total of 24,141 subjects, with a population-weighted mean age of 48.93 years. Over 30% of the subjects exhibited unhealthy sleep habits. Fully adjusted models revealed that both short sleep duration (HR=1.169, 95% CI 1.027-1.331) and long sleep duration (HR=1.286, 95% CI 1.08-1.531), were associated with an increased risk of all-cause mortality. The RCS curves showed a U-shaped relationship between sleep duration and risk of all-cause mortality. Subgroup analyses showed a significant association between poor sleep patterns and all-cause mortality among adults aged 26-64 years, males, and non-Hispanic whites. Furthermore, multinomial logistic regression identified several predictors associated with short and long sleep durations. Conclusion: Both short and long sleep duration are associated with an increased risk of all-cause mortality, with a U-shaped dose-response relationship. It is imperative to implement appropriate primary prevention strategies aimed at monitoring and providing health education to populations at risk of developing unhealthy sleep patterns.

Complementary and alternative medicine in relation to chemotherapy-induced peripheral neuropathy: A narrative review.

PURPOSE: To summarizes the available evidence on the effectiveness, safety, and feasibility of complementary and alternative medicine (CAM) in the management of chemotherapy-induced peripheral neuropathy (CIPN). METHODS: We searched for systematic reviews, and meta-analyzes published up to April 2023 in the Pubmed and Web of Science databases. The latest original research on related topics was also reviewed. The search was restricted to English-language papers. Two independent reviewers performed a quality assessment of the identified literature. RESULTS: The results of 35 systematic reviews and meta-analyzes were included in this study. Preliminary evidence suggests that CAM, including acupuncture, physical activity (PA), herbal and nutritional supplements, mind-body therapies, touch therapy, and non-invasive neuromodulation techniques, have shown tremendous potential for the prevention and treatment of CIPN. Of these, there is strong evidence supporting acupuncture, PA, and herbal medicine. However, existing clinical studies are also limited by the heterogeneity of study methods, insufficient sample size, and poor study design. Further studies are needed to validate the efficacy of CAM in patients with CIPN and to elucidate potential therapeutic mechanisms. CONCLUSIONS: Current research has reached a preliminary conclusion suggesting the potential efficacy of certain CAMs in the management of CIPN. Future clinical trials should incorporate more robust study design protocols and larger sample sizes to enhance the validity of findings.

Efficacy and Safety of Huangqi Guizhi Wuwu Decoction for Oxaliplatin-Induced Peripheral Neurotoxicity: A Systematic Review and Meta-Analysis.

Objective: Oxaliplatin is a first-line chemotherapy drug for the treatment of colorectal cancer, but its induced oxaliplatin-induced peripheral neurotoxicity (OIPN) affect the chemotherapy process and quality of life of tumor patients. OIPN is a serious and potentially permanent side effect of cancer treatment. Currently, no unified standard has been established for preventing and treating OIPN in Western medicine. Therefore, it is very important to seek effective prevention and treatment measures. Many clinical trials have reported that Huangqi Guizhi Wuwu decoction can effectively prevent OIPN, but substantial evidence base to support this treatment is lacking. We collected existing literature and evaluated the clinical efficacy and safety of Huangqi Guizhi Wuwu decoction for OIPN by performing a meta-analysis. Methods: We systematically searched China National Knowledge Internet (CNKI), VIP, Wan Fang Database, Pubmed, EMBASE, and Cochrane Library from inception through to Oct 2022 to identify only randomized controlled trials examining the prevention of OIPN using Huangqi Guizhi Wuwu decoction. This search was supplemented by manual retrieval, including dissertations and conference papers. All data were analyzed using RevMan 5.3 software. Results: A total of 18 papers involving 564 patients in the treatment group and 523 patients in the control group were included. A total of 17 articles reported the overall incidence of peripheral neurotoxicity (I² = 0%), and the overall incidence of peripheral neurotoxicity in the treatment group was 0.27 times higher than in the control group (95% CI: 0.20-0.36). A total of 16 articles reported the incidence of level III-IV severe peripheral neurotoxicity (I² = 0%), which was 0.16 times higher in the treatment group than in the control group (95% CI: 0.09-0.32). In the Huangqi Guizhi Wuwu VS no-interference subgroup, it showed that the incidence of severe peripheral neurotoxicity in the treat group was significantly lower than in the control group (OR:0.13, 95% CI:0.06-0.28). But in the Huangqi Guizhi Wuwu VS west medicine therapy subgroup, no significant difference between Huangqi Quizhi Wuwu and conventional Western medicine was observed for the prevention and treatment of severe OIPN (OR:0.37, 95% CI:0.09-1.53). A total of 2 articles were reported median nerve conduction velocity (I² = 51.2%); and no significant difference was found between the treatment and control groups (SMD: 1.43; 95% CI: 0.80-2.08); 4 studies showed Huangqi Guizhi Wuwu decoction did not increase the incidence of chemotherapy-related adverse reactions and was safe. Conclusions: Our current findings support the application of Huangqi Guizhi Wuwu decoction for the clinical prevention and treatment of patients with OIPN. However, high-quality RCT research is still needed to further exploration. The potential impact of Huangqi Guizhi Wuwu decoction on the quality of life or treatment compliance of cancer patients needs further research.

Identification and Validation of Key miRNAs for Colon Cancer Based on miRNA-Gene Integration Analysis.

Background: MicroRNAs (miRNAs) plays an essential role in the pathogenesis of colon cancer. This study aims to identify and verify key miRNAs that may serve as potential biomarkers for early diagnosis and treatment of colon cancer. Methods: Two miRNA microarray datasets (GSE53339 and GSE126093) were downloaded from the Gene Expression Omnibus (GEO) database, and the common differentially expressed miRNAs (DEMis) of both were identified by the "limma" package and the intersect function in R. Then, the miRwalk online tool was used to predict the target genes of the common DEMis and perform Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on those DEMis. The miRNA-gene network was constructed using Cytoscape software to identify key miRNAs and validated using quantitative real-time PCR (qRT-PCR) and The Cancer Genome Atlas (TCGA) dataset information for experimental and external database validation, respectively. In addition, we explored the correlation between key miRNAs and infiltrating immune cells and immunotherapy biomarkers. Results: Fourteen common DEMis were identified from the GEO database, and five targeted genes were predicted. A microRNA-gene network was subsequently constructed to identify three key miRNAs (miR-363-3p, miR-520e, and miR-330-5p). Both qRT-PCR and external database validation confirmed our findings. In addition, we found that miR-520e was significantly associated with infiltrating immune cells and established immune checkpoints. Conclusion: Our study identified three key miRNAs that influence the development of colon cancer. In addition, further studies suggest that infiltrating immune cells may play an essential role in the pathogenesis of colon cancer. These findings assist in early diagnosis and precision-targeted therapies.

Development and validation of the chemotherapy-induced peripheral neuropathy integrated assessment - oxaliplatin subscale: a prospective cohort study.

BACKGROUND: Current chemotherapy-induced peripheral neuropathy (CIPN) assessment tools mostly have poor sensitivity and weak anti-interference, so that it is sometimes difficult to provide substantive guidance for clinical intervention. This study aimed to develop an assessment tool dedicated for oxaliplatin to address these limitations. METHODS: This study screened 445 OIPN-related literatures for producing a symptom list, and developed the questionnaire module through expert supplement, item generation, content correlation analysis, pre-testing, and item improvement. The validation phase used a Chinese population-based prospective cohort study from June 2021 to July 2022. Patients were requested to complete the tested questionnaire, QLQ-CIPN20 and the CTCAE grading one day before cycles 2-6 of chemotherapy. Cronbach's α coefficient and intraclass correlation coefficient (ICC) were calculated for the internal consistency and stability analysis, respectively. Exploratory factor analysis was conducted to investigate the construct validity. The correlations among the tested questionnaire, QLQ-CIPN20 and CTCAE were compared for the criterion validity analysis. Wilcoxon signed-rank sum test was utilized to compare the sensitivity between the tested questionnaire and QLQ-CIPN20. RESULT: A 20-item CIPN assessment tool named chemotherapy-induced peripheral neuropathy integrated assessment - oxaliplatin subscale (CIPNIA-OS) was developed. The validation phase included 186 patients. Cronbach's α coefficient of CIPNIA-OS was 0.764 (> 0.7), and ICC was 0.997 (between 0.9 and 1). The structure of CIPNIA-OS containing seven factors was examined. The correlation coefficient between CIPNIA-OS and CTCAE was 0.661 (95%CI 0.623 to 0.695), which was significantly higher than that between QLQ-CIPN20 and CTCAE (0.417, 95%CI 0.363 to 0.469, p < 0.01). Besides, the total score of CIPNIA-OS was mostly higher than QLQ-CIPN20, with an average difference of 2.189 (CI 95% 2.056 to 2.322), and the difference gradually expanded with the progress of chemotherapy (p < 0.05). CONCLUSION: This study developed an original CIPN questionnaire which was dedicated for OIPN assessment. It was a comprehensive tool that covered acute OIPN symptoms and integrated features from several proven CIPN assessment tools. The validation results supported that CIPNIA-OS had satisfactory reliability, stability, construct, criterion validity, and was more accuracy and sensitive than QLQ-CIPN20 in the evaluation of OIPN.

Risk factors for advanced colorectal neoplasm in young adults: a meta-analysis.

Purpose: To evaluate the risk factors for young-onset advanced colorectal neoplasia. Methods: We performed a meta-analysis of 30 potential exposure risk factors from 28 original studies. Results: Several risk factors showed statistical significance, including male sex (odds ratio [OR]: 1.28; 95% CI: 1.12-1.47), metabolic syndrome (OR: 1.34; 95% CI: 1.25-1.44), hypertension (OR: 1.22; 95% CI: 1.17-1.28), diabetes (OR: 1.23; 95% CI: 1.15-1.32), inflammatory bowel disease (OR: 4.62; 95% CI: 1.12-17.54), obesity (OR: 1.23; 95% CI: 1.06-1.43), sedentary behavior (OR: 1.25; 95% CI: 1.06-1.48), smoking (OR: 1.19; 95% CI: 1.05-1.36), high alcohol consumption (OR: 1.37; 95% CI: 1.10-1.71), high intake of sugar (OR: 2.58; 95% CI: 1.61-4.13) and red meat (OR: 1.10; 95% CI: 1.04-1.16) and family history of colorectal cancer (OR: 3.14; 95% CI: 1.29-7.64). Conclusion: Our study identified potential risk factors for young-onset advanced colorectal neoplasms to help develop targeted primary prevention strategies.

Bibliometric analysis of global research on physical activity and sedentary behavior in the context of cancer.

Objective: Numerous studies focusing on sedentary behavior (SB) and physical activity (PA) in the context of cancer have been reported in recent years. We analyzed and visualized studies on SB and PA in patients with cancer over the last 20 years using scientometric methods, to provide insights on gaps and deficiencies in the literature, and to inform future research guidelines. Methods: All relevant studies in the field from 2001 to October 2022 were reviewed using bibliometric tools, including VOSviewer, Bibliometric online analysis platform, and biblioshiny, to determine the most influential countries, institutions, journals, and authors. We explored current research hotpots and potential research trends, based on keyword clustering and dynamic changes. Our research focuses on PA, SB, and cancer across the entire cancer continuum, from primary prevention to treatment to cancer survivorship. Results: Scientometric analysis identified 4,382 relevant manuscripts on SB and PA in the context of cancer, with a 10-fold increase in articles over the past 20 years. The United States, Canada, and Australia were the most influential countries. The journal, Supportive Care in Cancer, had the highest number of publications, while Clinical Oncology had the highest H-index. K.S. Courneya was the most influential author in this field, with the highest number of publications, total citations, and H-index. Keyword analysis revealed that current research is focused on PA and SB in patients with breast cancer, quality of life, and aerobic exercise. Future frontiers include cancer prehabilitation programs and cardiorespiratory fitness, and remote intervention and social support. Conclusion: By using bibliometrics, we conducted a comprehensive review of SB and PA in cancer-related studies. The current research focused on exercise and sedentariness in breast cancer patients and the role of PA in improving quality of life in survivorship. Emerging research foci were generally around cancer prehabilitation programs and remote intervention issues for PA. In addition, some publication deficits are noted: studies of PA and SB in less common cancers; the recommended doses and intensities of exercise for cancer; the timing of interventions for prehabilitation and the establishment of individualized exercise protocols. These deficiencies align with the needs for future research topics.

Data mining analysis reveals key acupoints and meridians for the treatment of chemotherapy-induced peripheral neuropathy.

OBJECTIVE: To explore effective acupoints and combinations for the treatment of chemotherapy-induced peripheral neuropathy (CIPN) METHODS: Clinical controlled trials and randomized controlled trials of acupuncture for CIPN were sourced from PubMed, Embase, Web of Science, and Chinese databases, including the Wanfang database, VIP Journals database, and China National Knowledge Infrastructure database. The quality of eligible research was evaluated based on CONSORT and STRICTA statements. The common acupoints, meridians, and acupoint combinations were determined from acupuncture prescriptions reporting positive effects and were analyzed using SPSS 23.0 and SPSS Modeler 14.1. Finally, a complex network was constructed using Cytoscape 3.8.2 to explore the core acupoints. RESULTS: The quality of 24 clinical trials was evaluated, and 20 acupuncture prescriptions that reported positive outcomes were included in subsequent data mining analysis. The most frequently used acupoints are ST36, LI11, LI4, LR3, and SP6. Meanwhile, they are also the core acupoints in acupuncture prescriptions according to the complex network with 28 nodes and 177 edges. The most commonly used meridians were the large intestine, stomach, and spleen. Acupoint combinations of LI11 and ST36, SP6 and ST36 were frequently used. CONCLUSION: Our study provides a reference for the selection of effective acupoints for CIPN treatment and a basis for the effective use of this form of traditional Chinese medicine. Furthermore, we found limitations in the design and implementation of the available clinical research, which should be minimized in future studies.

Effect of Shan Zha (Hawthorn or Crataegus) on gastrointestinal cancer: A network pharmacology and molecular docking study.

Background: Shan Zha (Hawthorn or Crataegus) is a traditional Chinese medicine (TCM) most commonly used for the treatment of hyperlipidemia. Gastrointestinal cancer is closely correlated with blood lipid levels. This study illustrates the potential anticancer effects of Shan Zha on gastrointestinal tumors based on network pharmacology and molecular docking. Methods: Hawthorn's bioactive ingredients and drug targets were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine version 2.0 (TCMIP v2.0), and Herbal Ingredients' Targets Platform (HIT 2.0) databases. Validated disease targets of gastrointestinal cancer were obtained from the Therapeutic Targets Database (TTD) and HIT 2.0 databases. Protein-protein interaction analysis of intersecting genes was performed using the Search Tool for the Retrieval of Interacting Genes (STRING) database. The functions of these genes were further analyzed by performing gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Molecular docking verification was performed using Molecular Operating Environment (MOE) software. Results: Four main bioactive components were identified in Shan Zha. A total of 271 potential drug targets were identified, and 393 gastrointestinal-tumor targets were obtained. Through protein interaction analysis of intersecting targets, the main components of Shan Zha were found to interact more closely with proteins such as tumor protein p53 (TP53), AKT serine/threonine kinase 1 (AKT1), JUN proto-oncogene (JUN), interleukin 6 (IL6), epidermal growth factor receptor (EGFR), and vascular endothelial growth factor A (VEGFA). KEGG pathway enrichment analysis showed a total of 127 pathways, mainly involving pathways in multiple types of cancer, the Phosphatidylinositol 3-kinase-Akt (PI3K-Akt) signaling pathway, and EGFR tyrosine kinase inhibitor resistance. Combined with The Cancer Genome Atlas (TCGA) differential analysis, key targets, including TP53, cyclin D1 (CCND1), EGFR, and VEGFA, were screened. Molecular docking results showed that quercetin and kaempferol had the good binding potential for TP53, CCND1, EGFR, and VEGFA. Conclusion: These findings suggest that Shan Zha exerts its effects on gastrointestinal cancers through a multitarget, multi-component, and a multi-pathway mechanism.

Disordered Gut Microbiota in Colorectal Tumor-Bearing Mice Altered Serum Metabolome Related to Fufangchangtai.

Purpose: This study aimed to investigate the relationship between gut microbiota (GM) and serum metabolism using antineoplastic Fufangchangtai (FFCT) as the model prescription in the treatment of colorectal cancer (CRC). Methods: Tumor-bearing mice and normal mice were administered different doses of FFCT. The tumor volume of tumor-bearing mice was observed. The levels of CD4+ and CD8+ T cells in the blood, spleen, and tumor of mice were determined using a flow cytometer. The bacterial microbiota in stool samples from mice and the serum metabolomics of FFCT-treated mice and fecal microbiota transplantation mice were detected using 16s RNA sequencing and liquid chromatography-mass spectrometry (LC/MS), respectively. Results: The tumor volume of mice showed no significant decrease after FFCT intervention. The levels of CD4+ and CD8+T lymphocytes showed a significant increase under the intervention of FFCT. GM of colorectal tumor-bearing mice and healthy mice were determined, and the diversity and abundance of Firmicutes, Deferribacteres, Bacteroidetes, and Proteobacteria were significantly different between the two groups. Furthermore, we found that the levels of matrine, isogingerenone B, and armillaripin were significantly decreased in tumor-bearing mice after FFCT intervention, indicating that the tumor-induced dysbiosis of gut bacteria may affect the absorption and metabolism of FFCT. Under the intervention of FFCT, serum metabolism of mice transplanted with feces from CRC patients showed less metabolites related to FFCT than that from healthy people, indicating that GM could be a single factor affecting the metabolism of FFCT. Furthermore, we found that different doses of FFCT-treated mice had higher abundance of Roseburia, Turicibacter, and Flexispira than that in the non-intervention control group. Firmicutes and Bacteroidetes in FFCT-treated groups showed a similar trend compared to the healthy group, indicating that FFCT might correct the intestinal microenvironment by modulating gut microbiota in colorectal tumor-bearing mice. Conclusion: The dysbiosis of GM in tumor-bearing mice reduced the serum metabolites related to FFCT, and FFCT could correct the disordered GM of colorectal tumor-bearing mice to exert efficacy.

Exploring the Mechanism of Weikang Keli in Inhibiting Gastric Cancer through the MAPK Signaling Pathway: Based on Network Pharmacology and Experimental Verification.

Background: With a high incidence and limited treatments, gastric cancer (GC) seriously threatens human health worldwide. Weikang Keli (WK) is a compound prescription summed up from clinical experience. In our previous studies, WK has been proved to exert antitumor effects. However, there are no research studies to discuss and verify its mechanism as a compound. Objective: The aim of the study is to explore the potential molecular mechanism of WK in the treatment of GC with the aid of network pharmacology and verify it through experiments. Methods: Related databases were used to obtain genes and targets of WK and gastric cancer. A protein-protein interaction (PPI) network is constructed and visualized by Cytoscape 3.7.2. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to analyze core targets. The cell viability of MFC and BGC-823 cells was determined by CCK8. Immunofluorescence was used to determine autophagy of GC cells. Moreover, the effect of WK on the MAPK signaling pathway in GC cells and tumor tissues of ICR mice was detected by Western blot. Results: A total of 106 cross targets of WK and GC were obtained. According to the enrichment analysis of GO and KEGG, we target the MAPK signaling pathway to discuss the mechanism of WK on GC. Cell experiments proved that WK inhibited the viability of gastric cancer cells in a dose-dependent and time-dependent manner. Autophagosome aggregation and an increase in the expression of an autophagy marker protein LC3-II can also be observed in WK groups. Further animal experiments showed that the tumor inhibition rate of WK showed a dose-effect relationship. Moreover, the expressions of p-JNK, p-p38, and p-ERR1/2 proteins in the MAPK signaling pathway in WK Group were downregulated both in the cell and animal experiments, compared with the blank control group. Conclusion: WK showed an explicit antitumor effect on gastric cancer through the MAPK signaling pathway, and the curative effect varies in different concentrations. Besides, in model mice, the antitumor effect of high-dose WK group is close to that of platinum. This study provided a theoretical basis for the application of WK in the clinical treatment of gastric cancer.

A risk scoring system to predict the individual incidence of early-onset colorectal cancer.

BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC) is increasing at an alarming rate and further studies are needed to identify risk factors and to develop prevention strategies. METHODS: Risk factors significantly associated with EOCRC were identified using meta-analysis. An individual risk appraisal model was constructed using the Rothman-Keller model. Next, a group of random data sets was generated using the binomial distribution function method, to determine nodes of risk assessment levels and to identify low, medium, and high risk populations. RESULTS: A total of 32,843 EOCRC patients were identified in this study, and nine significant risk factors were identified using meta-analysis, including male sex, Caucasian ethnicity, sedentary lifestyle, inflammatory bowel disease, and high intake of red meat and processed meat. After simulating the risk assessment data of 10,000 subjects, scores of 0 to 0.0018, 0.0018 to 0.0036, and 0.0036 or more were respectively considered as low-, moderate-, and high-risk populations for the EOCRC population based on risk trends from the Rothman-Keller model. CONCLUSION: This model can be used for screening of young adults to predict high risk of EOCRC and will contribute to the primary prevention strategies and the reduction of risk of developing EOCRC.

Diabetes mellitus as a risk factor for chemotherapy-induced peripheral neuropathy: a meta-analysis.

BACKGROUND: To identify the association between diabetes mellitus (DM) and the risk of chemotherapy-induced peripheral neuropathy (CIPN) through a systematic review and meta-analysis. METHODS: An electronic literature search was conducted in PubMed, Embase, Web of Science, the Wanfang database, the VIP Journals database (CQVIP), the China National Knowledge Infrastructure (CNKI) database, and the China Biology Medicine database (Sinomed) between January 2010 and January 2021. Articles were included if they investigated CIPN and DM. Stata 15.1 was used to analyze the data. RESULTS: We examined 8923 cancer patients from 25 studies comprising 9 cohort studies and 16 case-control studies. Meta-analysis showed that there was a statistically significant positive correlation between DM and CIPN (odds ratio [OR] = 1.60, 95% confidence interval [CI] = 1.38-1.85, P < 0.001). Egger's test (P = 0.824) showed no evidence of publication bias. The positive associations did not significant differ by study type, study quality, evaluation instrument, and type of antineoplastic drug. Omission of any single study had little effect on the combined risk estimate. Little evidence of heterogeneity was observed. CONCLUSION: This meta-analysis provides evidence of a significant positive association between DM and risk of CIPN. Furthermore, a more detailed evaluation is warranted for cancer patients with diabetes when they are treated with antineoplastic drugs that have the potential to cause peripheral neuropathy.

Platinum accumulation in oxaliplatin-induced peripheral neuropathy.

Oxaliplatin-induced peripheral neuropathy (OIPN) is a common and dose-limiting toxic effect that markedly limits the use of oxaliplatin and affects the quality of life. Although it is common, the underlying mechanisms of OIPN remain ambiguous. Recent studies have shown that the platinum accumulation in peripheral nervous system, especially in dorsal root ganglion, is a significant mechanism of OIPN. Several specific transporters, including organic cation transporters, high-affinity copper uptake protein1 (CTR1), ATPase copper transporting alpha (ATP7A) and multidrug and toxin extrusion protein 1 (MATE1), could be associated with this mechanism. This review summarizes the current research progress about the relationship between platinum accumulation and OIPN, as well as suggests trend for the future research.

Bibliometric Analysis Reveals a 20-Year Research Trend for Chemotherapy-Induced Peripheral Neuropathy.

OBJECTIVE: A lot of research has focused on the field of chemotherapy-induced peripheral neuropathy (CIPN). In this study, we performed a bibliometric analysis of CIPN-related publications to identify the key research areas and trends over the last 20 years. METHODS: We searched the Web of Science core collection for publications related to CIPN that were published between January 2001 and September 2021. We then performed bibliometric analysis and visualization using Microsoft Excel 2019, VOSviewer, and the Bibliometric online analysis platform (https://bibliometric.com/). RESULTS: In total, we identified 2,188 eligible publications in the field of CIPN, with an increasing trend in the annual number of publications. The United States and Italy were dominant in the CIPN field. Supportive Care in Cancer was the most productive journal. G. Cavaletti and A.A. Argyriou published the largest number of papers. Of all institutions, the University of Milano-Bicocca, Italy, published the highest number of papers. Analysis of the co-occurrence of keywords revealed the specific characteristics relating to the four main clusters: oxaliplatin, paclitaxel, pain management, and quality of life (QOL). Newly emerging research focusses predominantly on neuroinflammatory mechanisms and non-pharmacological interventions for CIPN. CONCLUSION: This bibliometric study reviewed the evolutionary trends in CIPN research and identified current research hotspots and research trends. In addition, we identified journals, institutions, and authors, with the highest levels of impact to enhance the collaboration and learning.

Exploring the Possible Mechanism and Drug Targets of Huang-Qi-Gui-Zhi-Wu-Wu Decoction for the Treatment of Chemotherapy-Induced Peripheral Neuropathy on Network Pharmacology.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of anticancer treatment, which may influence its successful completion. The Huang-Qi-Gui-Zhi-Wu-Wu decoction (HQGZWWD) has been widely used to treat CIPN in China although the pharmacological mechanisms involved have not been clarified. Using the network pharmacology approach, this study investigated the potential pathogenesis of CIPN and the therapeutic mechanisms exerted by the HQGZWWD herbal formula in CIPN. The targets of HQGZWWD were identified using traditional Chinese medicine (TCM) databases (TCMSP and ETCM) and prediction platforms (PharmMapper and TargetNet), and the genes of CIPN were collected by DisGeNET, GeneCards, and literature search. The common target interaction network between herbal formula and diseases was constructed by using Cytoscape. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to reveal the mechanism and efficacy of HQGZWWD in the treatment of CIPN. A total of 153 CIPN-related genes were screened, and a protein-protein interaction (PPI) network with 96 nodes and 424 edges was constructed. Sixty-three active components were retrieved from HQGZWWD, with a herb-composite compound-target network including 748 nodes and 5448 edges. Forty-one targets belong to the above two networks. The analysis of network results and literature review shows that the main pathological processes of CIPN may be the inflammatory response and nerve injury, and HQGZWWD plays a therapeutic role in CIPN by regulating inflammatory response and repairing nerve injury, thus verifying the reliable efficacy of this herbal formula. In addition, we found two new potential therapeutic targets (CDK7 and GSTM2) warranting further investigation. This study fully illustrates that TCM has the characteristics of a multicompound, multitarget, and multipathway treatment, which is of great significance to study the curative effect of herbal formulations.

Identification and Verification of Core Genes in Colorectal Cancer.

Colorectal cancer, a malignant neoplasm that occurs in the colorectal mucosa, is one of the most common types of gastrointestinal cancer. Colorectal cancer has been studied extensively, but the molecular mechanisms of this malignancy have not been characterized. This study identified and verified core genes associated with colorectal cancer using integrated bioinformatics analysis. Three gene expression profiles (GSE15781, GSE110223, and GSE110224) were downloaded from the Gene Expression Omnibus (GEO) databases. A total of 87 common differentially expressed genes (DEGs) among GSE15781, GSE110223, and GSE110224 were identified, including 19 upregulated genes and 68 downregulated genes. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed for common DEGs using clusterProfiler. These common DEGs were significantly involved in cancer-associated functions and signaling pathways. Then, we constructed protein-protein interaction networks of these common DEGs using Cytoscape software, which resulted in the identification of the following 10 core genes: SST, PYY, CXCL1, CXCL8, CXCL3, ZG16, AQP8, CLCA4, MS4A12, and GUCA2A. Analysis using qRT-PCR has shown that SST, CXCL8, and MS4A12 were significant differentially expressed between colorectal cancer tissues and normal colorectal tissues (P < 0.05). Gene Expression Profiling Interactive Analysis (GEPIA) overall survival (OS) has shown that low expressions of AQP8, ZG16, CXCL3, and CXCL8 may predict poor survival outcome in colorectal cancer. In conclusion, the core genes identified in this study contributed to the understanding of the molecular mechanisms involved in colorectal cancer development and may be targets for early diagnosis, prevention, and treatment of colorectal cancer.

The Identification and Verification of Key Long Noncoding RNAs in Ischemic Stroke.

Stroke is a neurological disease with high rates of mortality and disability. The pathogenesis of stroke is acute focal injury of the central nervous system, leading to impaired neural function. Ischemic stroke accounts for the majority of cases. At present, the exact molecular mechanism of ischemic stroke remains unclear. Studies have shown that long noncoding RNAs (lncRNAs) have an important regulatory role in biological processes, participating in the regulation of transcription and affecting the processing and splicing of mRNAs. Abnormal lncRNA expression is associated with various diseases, including diseases of the nervous system. To identify and verify the key lncRNAs in ischemic stroke, we downloaded gene expression data from the National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO) and obtain differentially expressed lncRNAs, miRNAs, and mRNAs by bioinformatics analysis. Cytoscape was used to reconstruct a lncRNA-miRNA-mRNA network on the basis of the competitive endogenous RNA theory. We performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of the mRNAs regulated by lncRNAs in the lncRNA-miRNA-mRNA network. The resulting lncRNA-miRNA-mRNA network was composed of 91 lncRNA nodes, 70 mRNA nodes, 21 miRNA nodes, and 288 edges. GO analysis and KEGG pathway analysis have shown that 191 GO terms and 23 KEGG pathways were enriched. Finally, we found that four key lncRNAs were highly correlated with ischemic stroke and could be used as potential new targets for treatment.