Adjuvant therapy with Huatan Sanjie Granules improves the prognosis of patients with primary liver cancer: a cohort study and the investigation of its mechanism of action based on network pharmacology.

Objective: Nowadays, primary liver carcinoma (PLC) is one of the major contributors to the global cancer burden, and China has the highest morbidity and mortality rates in the world. As a well-known Chinese herbal medicine (CHM) prescription, Huatan Sanjie Granules (HSG) has been used clinically for many years to treat PLC with remarkable efficacy, but the underlying mechanism of action remains unclear. Methods: A clinical cohort study was conducted to observe the overall survival of PLC patients with vs. without oral administration of HSG. Meanwhile, the BATMAN-TCM database was used to retrieve the potential active ingredients in the six herbs of HSG and their corresponding drug targets. PLC-related targets were then screened through the Gene Expression Omnibus (GEO) database. The protein-protein interaction (PPI) network of targets of HSG against PLC was constructed using Cytoscape software. The cell function assays were further carried out for verification. Results: The results of the cohort study showed that the median survival time of PLC patients exposed to HSG was 269 days, which was 23 days longer than that of the control group (HR, 0.62; 95% CI, 0.38-0.99; p = 0.047). In particular, the median survival time of Barcelona Clinic Liver Cancer stage C patients was 411 days in the exposure group, which was 137 days longer than that in the control group (HR, 0.59; 95% CI, 0.35-0.96; p = 0.036). Meanwhile, the enrichment analysis result for the obtained PPI network consisting of 362 potential core therapeutic targets suggest that HSG may inhibit the growth of liver cancer (LC) cells by blocking the PI3K-Akt/MAPK signaling pathways. Furthermore, the above prediction results were verified by a series of in vitro assays. Specifically, we found that the expressions TP53 and YWHA2, the targets of the hepatitis B virus signaling pathway, were significantly affected by HSG. Conclusion: HSG shows promising therapeutic efficacy in the adjuvant treatment of PLC.

Clinical characteristics and survival outcomes in patients aged 75 years or older with advanced colorectal cancer treated using traditional Chinese medicine: an observational retrospective study.

Limited evidence suggests that elderly patients with advanced colorectal cancer (ACRC) may benefit from traditional Chinese medicine (TCM). This study investigated the efficacy and safety of TCM in old ACRC patients treated in the Oncology Department of Xiyuan Hospital between January 2012 and December 2021. The clinical characteristics of these patients were retrospectively reviewed. Their progression-free survival (PFS) and total duration of TCM therapy (TTCM) were analyzed using the Kaplan-Meier curve. Forty-eight patients (F:M 13:35) with a mean age of 78.75 ± 2.99 years (range, 75-87) met the inclusion criteria. There were 18 cases of rectal cancer and 30 of colon cancer. The median PFS was 4 months (range, 1-26; 95% CI 3.26-4.73). The median TTCM was 5.5 months (range, 1-50; 95% CI 1.76-8.24). Subgroup analysis revealed that PFS and TTCM were shorter in patients with bone metastases and an ECOG performance status score of 2-3 (p < 0.05). No hematological toxicity or serious adverse reactions occurred during the study period. This real-world study demonstrates that TCM may be a potentially beneficial therapy for old ACRC patients, including when the ECOG performance status score is 2-3.

Efficacy of jianpi huatan granule in reducing colorectal cancer metastasis and recurrence after radical resection and adjuvant chemotherapy: Study protocol for a randomised, double-blind, placebo-controlled, multicentre trial.

Background: The high incidence and mortality rates of colorectal cancer (CRC) are a severe challenge in China. In patients with stage III and high-risk stage II CRC after radical resection and postoperative adjuvant chemoradiotherapy, 40-60% experience recurrence and metastasis. Several years of clinical practice have shown that traditional Chinese medicine, including Jianpi Huatan granule (JHG), effectively prevents stage III and high-risk stage II CRC recurrence and metastasis after radical resection and postoperative standard adjuvant chemotherapy. However, high-level systematic plans and evidence-based medicine are lacking in this regard. Therefore, this randomised control trial aimes to determine the efficacy of JHG in reducing stage III and high-risk stage II CRC metastasis and recurrence after radical resection and postoperative standard adjuvant chemotherapy. Methods: This is a multicentre, randomised, double-blind, placebo-controlled clinical trial. Three hundred and fifty patients with stage III or high-risk stage II CRC who completed adjuvant chemotherapy after radical resection will be recruited from eight medical centres in China and randomly assigned to test (n = 175) and control (n = 175) groups at a ratio of 1:1. The test group will receive oral JHG for 3 months, whereas the control group will receive oral placebo for 3 months. The primary outcomes will be the disease-free survival and 1-, 2-, and 3-years metastasis and recurrence rates, whereas the secondary outcomes will be quality of life and circulating tumour cells. The patients will be followed-up monthly during treatment and every 3-6 months thereafter until recurrence, metastasis, death, or the end of the study. Trial registration: This trial was registered at ClinicalTrials.gov (NCT03716063).

A meta-analysis of the value of circulating tumor cells in monitoring postoperative recurrence and metastasis of colorectal cancer.

OBJECTIVE: Circulating tumor cells (CTCs) as novel biomarkers are widely investigated in various cancers, although most of the literature shows that CTCs have predictive value for recurrence, metastasis, and prognosis after CRC surgery, results remain controversial. We aimed to systematically evaluate the value of CTCs in monitoring of colorectal cancer (CRC) recurrence and metastasis after surgery. METHOD: The PubMed, Cochrane Library, Embase, and other databases were searched from the establishment of the database to May 27, 2021. Relevant literature searches and data extraction were performed independently by two reviewers. The quality assessment was performed using the QUADAS2 scale developed by the Cochrane collaboration. The heterogeneity was checked using the Spearman correlation coefficient and the Cochran-Q test in the Meta-Disc1.4 software. Subgroup analysis was used to explore the source of heterogeneity. Considering that all the included papers were clinical studies with clinical heterogeneity, random effect model was adopted for analysis. And the sensitivity (Sen), specificity (Spe), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) curves of CTCs, in monitoring recurrence and metastasis after CRC, were calculated. The publication bias of the included studies was assessed using Deek's funnel figure. RESULT: The literature included a total of 13 articles, comprising 1788 cases, and the overall quality of the literature was high. After summing up the indicators, the sensitivity pooled-value of the peripheral blood CTCs to monitor the recurrence and metastasis value of CRC after CRC was 0.67 [95%CI (0.62, 0.71)], specificity pooled-value was 0.71 [95%CI (0.67, 0.72)], PLR pooled-value was 2.37 [95%CI [1.52, 3.71]), NLR pooled into 0.53 [95%CI (0.36, 0.78)], DOR pooled into 4.97 [95%CI (2.11, 11.72)], AUC was 0.7395. CONCLUSION: Peripheral blood CTCs have a moderate monitoring value for recurrence and metastasis after CRC; CTCs detected one week after surgery may be more correlated with recurrence and metastasis.

Impact of cancer types on COVID-19 infection and mortality risk: a protocol for systematic review and meta-analysis.

INTRODUCTION: The COVID-19 pandemic has created a huge social and economic burden, and the lifestyles of individuals have significantly changed. In addition, the diagnosis, treatment and management of patients with cancer were greatly affected. Studies have shown that patients with cancer are at a higher risk of COVID-19 infection-related complications, which require aggressive preventive measures. Different types of cancer may have different risks of COVID-19 infection and death, and different preventive care measures are needed for different types of patients with cancer. Here, we designed a protocol for systematic review and meta-analysis to explore the impact of cancer types on COVID-19 infection and mortality risk. METHODS AND ANALYSIS: A systematic search plan will be performed to filter the eligible studies in the seven databases, namely PubMed, Cochrane search strategy, EMBASE search strategy, SinoMed, China National Knowledge Infrastructure, China Science and Technology Journals Database, and Wanfang database from 2019 to 10 August 2021. Two independent reviewers will choose the eligible studies and extract the data. The risk of bias will be evaluated based on the Newcastle-Ottawa Scale recommended by the Cochrane Collaboration. Finally, a systematic review and meta-analysis will be performed using Review Manager (V.5.3) statistical software. ETHICS AND DISSEMINATION: Formal ethical approval is not required, and the findings will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42021271108.

Statins use and the prognosis of colorectal cancer: a meta-analysis.

BACKGROUND: Previous observational studies regarding the prognostic value of statin on colorectal cancer (CRC) patients showed various results. METHODS: Articles regarding the prognostic value of statin on CRC and published in English and before October 2020 were searched in the following databases: PubMed, Web of Science, EMBASE, Medline and Google Scholar. The multivariate hazard ratios (HRs) and their 95% confidence intervals (CI) were computed to explore associations between statins use and overall mortality or cancer-specific mortality of CRC. RESULTS: The study included 5 retrospective case-control studies (including 475 statins users and 1925 no-statin users) and 11 prospective cohort studies (including 40659 statins users and 344459 no-statin users). The present study showed that statins use might be significantly associated with lower overall mortality in CRC with a random effects model (HR = 0.81, 95% CI 0.76 to 0.86, I2 = 61.9%, p value for Q test <0.001). In addition, statins use might be significantly associated with lower cancer-specific mortality in CRC with a random effects model (HR = 0.78, 95% CI 0.72 to 0.85, I2 = 57.3%, p value for Q test = 0.007). CONCLUSIONS: In conclusion, the present study indicated that that statin use was a protective factor for CRC prognosis. However, the relationship between statins use and CRC prognosis requires repeated and large prospective studies to be verified.

Effectiveness and Safety Evaluation of Chinese Medicine in Treatment of Metastatic Colorectal Cancer after Chemotherapy Failure: Protocol of a Prospective Multicenter Cohort Study.

BACKGROUND: Colorectal cancer (CRC) is the second most common cause of cancer-related deaths and has the third highest incidence in the world. Almost half of the patients with CRC have metastases at the time of diagnosis. However, the treatment for patients with metastatic CRC that progresses after approved conventional chemotherapy is still controversial. Chinese medicine (CM) has unique characteristics and advantages in treating metastatic CRC. OBJECTIVE: To assess the effectiveness and safety of CM in patients with metastatic CRC after failure of conventional chemotherapy. METHODS: The study is a multicenter prospective cohort study. A total of 384 patients with documented metastatic CRC after failure of conventional chemotherapy will be included from 9 hospitals among Beijing, Shanghai, Nanjing, and Guizhou, and assigned to three groups according to paitents' wishes: (1) integrated Chinese and Western medicine (ICM) group receiving CM herbal treatment combined with Western medicine (WM) anti-tumor therapy, (2) Chinese medicine (CM) group receiving only CM herbal treatment, and (3) WM group receiving only WM anti-tumor therapy. The primary endpoint is the overall survival (OS). Secondary endpoints include the progression free survival (PFS), quality of life (QOL) assessed by the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) questionnaire, tumor control, and CM symptom score. DISCUSSION: This prospective study will assess the effectiveness and safety of CM in treating metastatic CRC after conventional chemotherapy failure. Patients in the ICM group will be compared with those in the WM group and CM group. If certified to be effective, national provision of CM treatment in metastatic CRC will probably be advised. (Registration No. NCT02923622 on ClinicalTrials.gov).

[Systematic review and Meta-analysis of Shenqi Fuzheng injection combined with first-line chemotherapy for non-small cell lung cancer].

The paper is to systematically evaluate the effect and safety of Shenqi Fuzheng injection (SFI) combined with first-line chemotherapy for non-small cell lung cancer (NSCLC). Randomized controlled trials (RCTs) on Shenqi Fuzheng injection (SFI) combined with first-line chemotherapy (experiment group) and chemotherapy alone group ( control group) were electronically retrieved from Medline, EMbase, Clinical Trials, Cochrane Library, CBM, CNKI, VIP, and Wanfang Data base. All trials were assessed for quality according to the Cochrane Reviewer's Handbook for Systematic Reviews of Intervention and then Meta-analysis was performed withRevMan5. 2 Software. A total of 43 RCTs (3433 patients) were included after screening and selecting. Results of Meta-analysis showed that: Objective remission rate (ORR): ORR of experimental group was about 20% higher than that of control group [RR = 1.23, 95% CI (1.11,1.35), P < 0.0001]. Disease control rate (DCR):DCR of SFI combined with first-line chemotherapy was 11% higher than that of first-line chemotherapy alone [RR = 1.11, 95% CI (1.07, 1.16), P < 0.000 01]. Life quality evaluated by Kosovan performance status (KPS) showed that: life quality improvement rate of experimental group was about twice of that in control group [RR = 2.02, 95% CI (1.81, 2.26), P < 0.000 01]. Toxic and side reaction analysis showed that: the incidence of side reactions in experimental group was about 50% lower than that in control group [RR = 0.59, 95% CI (0.53, 0.66), P < 0.000 01]. Immune function test showed that: the function of experimental group was 3.2 (standard deviations) times greater than that of control group [MD = 3.23, 95% CI (2.86, 3.60), P < 0.000 01]. We can see that SFI combined with first-line chemotherapy for NSCLC can increase objective efficacy, improve life quality, decrease toxic and side reactionsinduced by chemotherapy, and improve the immune functions. As most of the included studies in this systematic evaluation had poor quality, the evidence to support conclusion was weak, so it was necessary to conduct more multi-center clinical trials with high quality methods and rigorous design.