A Bibliometric Analysis of Metabolic Reprogramming in the Tumor Microenvironment From 2003 to 2022.

BACKGROUND: Despite considerable progress in cancer immunotherapy, it is not available for many patients. Resistance to immune checkpoint blockers arises from the intricate interactions between cancer and its microenvironment. Metabolic reprogramming in tumor and immune cells in the tumor microenvironment (TME) influences anti-tumor immune responses by remodeling the immune microenvironment. Metabolic reprogramming has emerged as an important hallmark of tumorigenesis. However, few studies have focused on the TME and metabolic reprogramming. Therefore, we aimed to explore the current research status and popular topics in TME-related metabolic reprogramming over a 20 years using a bibliometric approach. METHODS: Studies focusing on metabolic reprogramming and TME were searched using the Web of Science Core Collection database. Bibliometric and visual analyses of the articles and reviews were performed using Bibliometrix, VOSviewer, and CiteSpace. RESULTS: In total, 4726 articles published between 2003 and 2022 were selected. The number of publications and citations has increased annually. Cooperation network analysis indicated that the United States holds the foremost position in metabolic reprogramming and TME research with the highest volume of publications and citations, thus exerting the greatest influence. Among these institutions, Fudan University displayed the highest level of productivity. Frontiers in Immunology showed the highest degree of productivity in this field. Ho Ping-Chih made the most article contributions, and Pearce Edward J. was the most co-cited author. Four clusters were obtained after a cluster analysis of the authors' keywords: TME, metabolic reprogramming, immunometabolism, and immunity. Immunometabolism, glycolysis, immune cells, and tumor-associated macrophages are relatively recent keywords that have attracted increasing attention. CONCLUSIONS: A comprehensive landscape of advancements in metabolic reprogramming and the TME was evaluated, which provided crucial information for scholars to further advance this promising field. Further research should explore new topics related to immunometabolism in the TME using a transdisciplinary approach.

Immortal Time Bias-Corrected Effectiveness of Traditional Chinese Medicine in Non-Small Cell Lung Cancer (C-EVID): A Prospective Cohort Study.

Background: Relatively little is known about the effect of traditional Chinese medicine (TCM) on prognosis of non-small cell lung cancer (NSCLC). Methods: In this nationwide, multicenter, prospective, cohort study, eligible patients aged 18-75 years with radical resection, and histologically confirmed stage II-IIIA NSCLC were enrolled. All patients received 4 cycles of standard adjuvant chemotherapy. Patients who received Chinese herbal decoction and (or) oral Chinese patent medicine for a cumulative period of not less than 6 months were defined as TCM group, otherwise they were considered as control group. The primary endpoint was DFS calculated using the Kaplan-Meier method. A time-dependent Cox proportional hazards model was used to correct immortal time bias. The secondary endpoints included DFS in patients of different characteristics, and safety analyses. This study was registered with the Chinese Clinical Trial Registry (ChiCTR1800015776). Results: A total of 507 patients were included (230 patients in the TCM group; 277 patients in the control group). The median follow-up was 32.1 months. 101 (44%) in the TCM group and 186 (67%) in the control group had disease relapse. The median DFS was not reached in the TCM group and was 19.4 months (95% CI, 14.2 to 24.6) in the control group. The adjusted time-dependent HR was 0.61 (95% CI, 0.47 to 0.78), equalling to a 39% reduction in the risk of disease recurrence with TCM. the number needed to treat to prevent one patient from relapsing was 4.29 (95% CI, 3.15 to 6.73) at 5 years. Similar results were observed in most of subgroups. Patients had a significant improvement in white blood cell decrease, nausea, decreased appetite, diarrhea, pain, and fatigue in the TCM group. Conclusion: TCM may improves DFS and has a better tolerability profile in patients with stage II-IIIA NSCLC receiving standard chemotherapy after complete resection compared with those receiving standard chemotherapy alone. Further studies are warranted.

UGT1A1 Allele Test Not Only Minimizes the Toxicity But Also Maximizes the Therapeutic Effect of Irinotecan in the Treatment of Colorectal Cancer: A Narrative Review.

Background: Irinotecan is a first-line agent in the systematic treatment of colorectal cancer (CRC). Adjusting the dose of irinotecan according to the uridine diphosphate glucuronosyltransferase (UGT) 1A1 genotype reflects the principle of individualized and precision medicine, and may improve the chemotherapy response and survival of CRC. Methods: To summarize the feasibility, efficacy and safety of high dose irinotecan in CRC patients with UGT1A1 wild-type or heterozygous alleles, PubMed, EMBASE, MEDLINE and the Cochrane Central Register of Controlled Trials online databases were searched from the date of creation to October 22, 2021. Results: A total of 1,186 related literatures were searched, and 14 studies were included for review according to the inclusion criteria. The results indicated that the maximum tolerated dose of irinotecan in CRC patients with UGT1A1 wild-type or heterozygous variant was significantly higher than the conventional recommended dose. Chemotherapy based on high dose irinotecan improved the clinical efficacy in mCRC patients with UGT1A1*28 wild-type and heterozygous variant, and the toxicity was tolerated, as reflected in most studies. Conclusions: We are optimistic about the application of high dose irinotecan for mCRC patients with UGT1A1*28 wild-type or heterozygous variant, which will provide a relatively clear direction for future research and certain norms for clinical practice.

Efficacy and safety of TCM combined with chemotherapy for SCLC: a systematic review and meta-analysis.

BACKGROUND: Chemotherapy is the standard treatment for small cell lung cancer (SCLC), but chemotherapy resistance and adverse reactions remain major problems. Although Traditional Chinese Medicine (TCM) is wildly applied for patients with SCLC in China, the evidence of TCM in the treatment for SCLC is limited. PURPOSE: To evaluate the efficacy and safety of TCM combined with chemotherapy for patients with SCLC. METHOD: We conducted a systematic search of PubMed, EMBASE, the Chinese National Knowledge Infrastructure, the VIP Information Database, and the Wanfang Database for randomized-controlled trials (RCTs) that are relevant. The included studies were reviewed by two investigators, with relevant data extracted independently. The effect estimate of interest was the relative risk (RR) or mean difference with 95% confidence intervals (95% CIs). RESULTS: 22 RCTs involving 1887 patients were included in this study. Compared with patients treated with chemotherapy© alone, those with Chinese herbal medicine and chemotherapy (TCM-C) had better therapeutic effects (RR = 1.295, 95% CI 1.205-1.391, P < 0.001), KPS scores (RR = 1.310, 95% CI 1.210-1.418, P < 0.001), 1-year survival rate (RR = 1.282, 95% CI 1.129-1.456, P < 0.001), 3-year survival rate (RR = 2.109, 95% CI 1.514-2.939, P < 0.001), and 5-year survival rate (RR = 2.373, 95% CI 1.227-4.587, P = 0.01). The incidence of gastrointestinal reaction (RR of = 0.786, 95% CI 0.709-0.870, P < 0.000) and bone marrow depression (RR = 0.837, 95% CI 0.726-0.965, P = 0.014) in TCM-C group were lower than that in the C group. CONCLUSION: The systematic review indicated that TCM combined with chemotherapy may improve therapeutic effect, quality of life, and prolong survival time. More large-scale and higher quality RCTs are warranted to support our findings. PROSPERO REGISTRATION NUMBER: CRD42016038016.

Prognostic significance of E-cadherin expression in prostatic carcinoma: A protocol for systematic review and meta-analysis.

BACKGROUND: Increasing studies were performed to explore the prognostic value of E-cadherin in prostatic carcinoma, however, with inconsistent results. Hence, this systematic review is aimed to evaluate the prognostic role of E-cadherin in patients with prostatic carcinoma (PCa). METHODS: A comprehensive literature search in all available databases will be conducted to identify eligible studies. We will employ hazard ratios (HRs) and 95% confidence intervals (95% CIs) to estimate the correlations between E-cadherin expression and overall survival (OS), disease-free survival (DFS), relapse-free survival (RFS), progression-free survival (PFS) and clinicopathological features. Meta-analysis will be performed using Review Manager (Revman) 5.3.5 software (Cochrane Community, London, United Kingdom) and STATA 14 software (version 14.0; Stata Corp, College Station, TX). RESULTS: This study will provide a high-quality synthesis of current evidence of the correlations between snail expression and OS, DFS/RFS, PFS and clinicopathological features. CONCLUSION: The study will provide updated evidence to assess whether the expression of E-cadherin is in association with poor prognosis in patients with PCa. ETHICS AND DISSEMINATION: It is not necessary for ethical approval because individuals cannot be identified. The protocol will be disseminated in a peer-reviewed journal or presented at a relevant conference. PROSPERO REGISTRATION NUMBER: This systematic review protocol has been registered in the PROSPERO network (No. CRD42019128353).

Study on the treatment of pancreatic cancer with integrated traditional Chinese and Western medicine: A study protocol of a multicenter prospective cohort study.

INTRODUCTION: Pancreatic cancer is one of the most lethal malignancies worldwide. Most patients are diagnosed at an advanced stage, which leads to a poor prognosis and a low survival rate. At present, treatment options for pancreatic cancer are limited, so it is vital to explore new treatments and strategies. Traditional Chinese medicine (TCM) is an important method for cancer prevention and treatment in China. We will conduct a multicenter, prospective cohort study to evaluate the survival and quality of life of patients with advanced pancreatic cancer treated with integrated traditional Chinese and Western medicine, further refine the core pathogenesis of TCM for pancreatic cancer, form a core prescription, and provide clinical data support for the clinical plan of integrated treatment of pancreatic cancer using Chinese and Western medicine; this will aid in the development of the best comprehensive treatment plan for patients. METHODS AND ANALYSIS: This study will recruit patients with stage 3 to 4 pancreatic cancer in 12 medical units from April 2019 to June 2020. Patients will be divided into a Western medicine treatment group and an integrated traditional Chinese and Western medicine treatment group, with a total of 148 patients. Overall survival is the main efficacy index, while the secondary efficacy indexes are progression-free survival, tumor markers, TCM symptom grading scale, quality of life assessment, Eastern Cooperative Oncology Group (ECOG) score, and imaging assessment. A follow-up will be performed every 6 weeks ±1 week. The end point is the death of the patient or the end of the study (October 31, 2021). Statistical analysis will be performed using Statistical Packages of Social Sciences software (SPSS). ETHICS AND DISSEMINATION: This work was supported by Beijing Municipal Science and Technology Commission and approved by the ethics committee of Guang'anmen Hospital, China Academy of Chinese Medical Sciences (Approval No. 2019-016-KY). All patients will sign a written informed consent prior to data collection. The results will be disseminated through peer-reviewed journals and conference presentations and will be openly shared after completion of the trial. TRIAL REGISTRATION: The trial was registered with the Chinese Clinical Trials Registry (ChiCTR1900022632, pre-registration).

Taxane-based chemotherapy and risk of breast cancer-related lymphedema: Protocol for a systematic review and meta-analysis.

BACKGROUND: Many studies were performed to explore the correlation between taxane-based chemotherapy and the risk of breast cancer-related lymphedema (BCRL), however, with inconsistent results. Hence, the purpose of this study is to evaluate whether taxane-based chemotherapy is a risk factor for BCRL. METHODS: A comprehensive systematic search of clinical trials published in the PubMed, Embase and the Cochrane Library databases will be conducted to identify eligible studies up to the date of December 31, 2018. We will employ risk ratios with 95% confidence intervals (95% CIs) to estimate the correlations between taxane-based chemotherapy and BCRL. Meta-analysis will be performed using Stata SE version 12.0 software. RESULTS: The results of this systematic review and meta-analysis will provide a high-quality synthesis of existing evidence of the correlations between taxane-based chemotherapy and the risk of BCRL. CONCLUSION: The protocol will provide updated evidence for the use of taxane-based chemotherapy in postoperative breast cancer patients. ETHICS AND DISSEMINATION: It is not necessary for ethical approval because it is based on published studies. The protocol will be disseminated in a peer-reviewed journal or presented at a topic-related conference. TRIAL REGISTRATION: This systematic review protocol has been registered with a number of CRD42019123989.

Prognositic significance of P-cadherin expression in breast cancer: Protocol for a meta-analysis.

BACKGROUND: P-cadherin is a calcium-dependent cell-cell adhesion glycoprotein. It has been implicated in invasiveness and metastasis. However, the clinical prognostic value of overexpression of P-cadherin in patients with breast cancer (BC) remains unsettled. METHODS: A systematic literature search will be performed in all available databases to quantitatively review eligible studies and identify all relevant data, which could be used to detect the relationship between overexpression of P-cadherin and overall survival (OS), disease-free survival (DFS), and clinicopathological parameters. Hazard ratio and 95% confidence intervals (CIs) or P value will be employed as effect measures to estimate the correlation between P-cadherin and the oncologic outcomes including overall survival (OS), disease-free survival (DFS). Odds ratios (ORs) and the 95% CIs will be evaluated for the pooled analysis of the correlation between P-cadherin expression and clinicopathological features. We will use the Review Manager (Revman) 5.3.5 software (Cochrane Community, London, United Kingdom) and STATA 14 software (version 14.0; Stata Corp, College Station, TX) to perform the meta-analysis to calculate the data. RESULTS: The review will provide a high-quality synthesis of current evidence of the prognostic role of P-cadherin in BCs. The results will be published in a peer-reviewed journal. CONCLUSION: We hope that the results of this study will provide significant evidence to assess whether the expression of P-cadherin is associated with poor prognosis in patients with BC. PROSPERO REGISTRATION NUMBER: This meta-analysis protocol has been registered in the PROSPERO network with registration number: CRD42019119880.

TCM therapies combined with chemotherapy for preventing recurrence and metastasis in postoperative II to IIIA NSCLC: A protocol for a systematic review and meta-analysis.

BACKGROUND: Traditional Chinese Medicine (TCM) therapies have been combined with chemotherapy for preventing Recurrence and metastasis in postoperative II to IIIA non-small-cell lung cancer (NSCLC) and the associated better disease-free survival (DFS), but its effects remain elusive. The purpose of this review is to assess the efficacy of TCM therapies as a treatment for postoperative II to IIIA NSCLC. METHODS AND ANALYSIS: Seventh databases will be searched for relevant studies from inception to the present date. We will include randomized controlled trials assessing TCM therapies combined with chemotherapy for preventing Recurrence and metastasis in postoperative II to IIIA NSCLC. The methodological qualities, including the risk of bias, will be evaluated using the Cochrane risk of bias assessment tool, while confidence in the cumulative evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. ETHICS AND DISSEMINATION: Ethical approval is not required, as this study is based on the review of published research. This review will be published in a peer-reviewed journal and disseminated both electronically and in print. PROSPERO REGISTRATION NUMBER: The protocol for this systematic review has been registered on PROSPERO under the number CRD42019116594.

Cinobufacini Injection Improves the Efficacy of Chemotherapy on Advanced Stage Gastric Cancer: A Systemic Review and Meta-Analysis.

Gastric cancer has a high morbidity and mortality. Chemotherapy regimens are routine advanced stage gastric cancer (AGC) treatment protocols, but most of these drugs have side-effects such as myelosuppression and gastrointestinal disorders. Cinobufacini, an extractive from TCM, could suppress cell proliferation and inhibit gastric cancer. In this study, we comprehensively reviewed the literature on the efficacy comparison between Cinobufacini injection combined with chemotherapy and chemotherapy solely used in AGC treatment. We extracted data for from six electronic databases to evaluate the efficacy of Cinobufacini injection on AGC patients. Twelve studies with a total of 853 patients were finally included in our study. The results indicated that Cinobufacini injection could increase response rate and disease control rate of chemotherapy on AGC, improve the life quality of AGC patients, increase leukocytes, improve anemia, improve hand-foot syndrome induced by chemotherapy, and relieve cancer pain. This study has its own limitations that prevented us from drawing a definite conclusion and more well-designed clinical trials of TCM are needed.

Endoscopic Screening in Asian Countries Is Associated With Reduced Gastric Cancer Mortality: A Meta-analysis and Systematic Review.

BACKGROUND & AIMS: It is not clear how endoscopic screening for gastric cancer affects incidence or mortality. We performed a systematic review and meta-analysis to evaluate the relationship between endoscopic screening for gastric cancer and mortality and incidence. METHODS: We conducted a systematic search of PubMed and EMBASE for published cohort and case-control studies of adults without gastric cancer who underwent endoscopic screening at least once that included a comparator and reported outcomes of mortality or incidence through March 8, 2018. Two investigators independently reviewed the included studies and extracted relevant data. The effect estimate of interest was the relative risk (RR). We used a random effects model to combine RRs and 95% confidence intervals (Cis). RESULTS: Our final analysis included 6 cohort studies and 4 nested case-control studies comprising 342,013 individuals, all from Asia. The combined result (RR, 0.60; 95% CI, 0.49-0.73) indicated that endoscopic screening was associated with a 40% RR reduction in gastric cancer mortality. We did not observe an association between endoscopic screening and incidence (RR, 1.14; 95% CI, 0.93-1.40). Subgroup analysis showed significant reductions in gastric cancer mortality after endoscopic screening compared with no screening (RR, 0.58; 95% CI, 0.48-0.70) or radiographic screening (RR, 0.33; 95% CI, 0.12-0.91). However, endoscopic screening did not significantly reduce mortality compared with expected deaths (RR, 0.67; 95% CI, 0.38-1.16). CONCLUSIONS: In a systematic review and meta-analysis, we found that endoscopic screening may reduce the risk of death from gastric cancer and not affect incidence in Asian countries. Population-based prospective cohort studies are warranted to confirm our findings.

Chinese Herbal Medicine for Postpartum Depression: A Systematic Review of Randomized Controlled Trials.

Background. Postpartum depression (PPD) does great harm to women following childbirth. The aim of this study was to conduct a systematic review of the literature to assess the efficacy and safety of CHM for the treatment of PPD. Methods. Published or ongoing registered trials were searched for from the inception of the various databases to December 31, 2015. Data extraction and methodology assessment were conducted independently by two researchers. RevMan 5.3 software was used to analyze the data. Results. Forty-seven registered clinical trials (RCTs) were identified and reviewed. The results showed CHM alone or in combination with routine treatments could reduce HAMD score, EPDS score, incidence of adverse events, TESS, and SERS. CHM combined with routine treatment was more effective in increasing serum estradiol levels and reducing progesterone levels than routine treatment alone. Meanwhile, pooled data revealed that MRLQS combined with routine treatments or MRLQS plus MSHS combined with routine treatments were more effective than other therapeutic methods in TCM. MRLQS plus MSHS alone was found to be an effective alternative when compared to routine treatments. Conclusions. This review suggested that CHM was safe and effective in the treatment of PPD. However, this could not be proven conclusively. To ensure evidence-based clinical practice, more rigorously designed trials are warranted.

Wendan decoction (温胆汤) for treatment of schizophrenia: a systematic review of randomized controlled trials.

OBJECTIVE: To assess the beneficial and adverse effects of Wendan Decoction (温胆汤, WDD) for the treatment of schizophrenia. METHODS: Five electronic databases were searched until May 2014, including the Chinese National Knowledge Infrastructure, the Chinese Biomedical Literature Database, the Chinese Scientist Journal Database, PubMed, and the Cochrane Central Register of Controlled Trials in the Cochrane Library. The randomized controlled trials (RCTs) testing WDD against placebo, antipsychotic drugs, or WDD combined with antipsychotic drugs against antipsychotic drugs alone were included. Study selection, data extraction, quality assessment, and data analyses were conducted according to the Cochrane standards. RESULTS: Thirteen RCTs (involving 1,174 patients) were included and the methodological quality was evaluated as generally low. The pooled results showed that WDD combined with antipsychotic drugs were more effective in clinical comprehensive effect, Positive and Negative Syndrome Scale (PANSS) scores and Brief Psychiatric Rating Scale scores compared with antipsychotic drugs alone. However, WDD had less effectiveness compared with antipsychotics in clinical comprehensive effect; and WDD was not different from antipsychotic drugs for PANSS scores. The side effects were significantly reduced in the intervention group compared with the control group. CONCLUSIONS: WDD appears to be effective on improving symptoms in patients with schizophrenia. However, due to poor methodological quality in the majority of the included trials, the potential benefit from WDD needs to be confirmed in rigorous trials and the design and reporting of trials should follow the international standards.