The exploration of mitochondrial-related features helps to reveal the prognosis and immunotherapy methods of colorectal cancer.

BACKGROUND: Cancer cell survival, proliferation, and metabolism are all intertwined with mitochondria. However, a complete description of how the features of mitochondria relate to the tumor microenvironment (TME) and immunological landscape of colorectal cancer (CRC) has yet to be made. We performed subgroup analysis on CRC patient data obtained from the databases using non-negative matrix factorization (NMF) clustering. Construct a prognostic model using the mitochondrial-related gene (MRG) risk score, and then compare it to other models for accuracy. Comprehensive analyses of the risk score, in conjunction with the TME and immune landscape, were performed, and the relationship between the model and different types of cell death, radiation and chemotherapy, and drug resistance was investigated. Results from immunohistochemistry and single-cell sequencing were utilized to verify the model genes, and a drug sensitivity analysis was conducted to evaluate possible therapeutic medicines. The pan-cancer analysis is utilized to further investigate the role of genes in a wider range of malignancies. METHODS AND RESULTS: We found that CRC patients based on MRG were divided into two groups with significant differences in survival outcomes and TME between groups. The predictive power of the risk score was further shown by building a prognostic model and testing it extensively in both internal and external cohorts. Multiple immune therapeutic responses and the expression of immunological checkpoints demonstrate that the risk score is connected to immunotherapy success. The correlation analysis of the risk score provide more ideas and guidance for prognostic models in clinical treatment. CONCLUSION: The TME, immune cell infiltration, and responsiveness to immunotherapy in CRC were all thoroughly evaluated on the basis of MRG features. The comparative validation of multiple queues and models combined with clinical data ensures the effectiveness and clinical practicality of MRG features. Our studies help clinicians create individualized treatment programs for individuals with cancer.

Traditional Chinese medicines and capecitabine-based chemotherapy for colorectal cancer treatment: A meta-analysis.

This meta-analysis was conducted to evaluate the efficacy and safety of the addition of Traditional Chinese Medicine (TCMs) to capecitabine-based regimens for colorectal cancer (CRC) in term of tumor. The eight electronic databases including Cochrane Library, PubMed, Web of Science (WOS), Excerpt Medica Database (Embase), Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Journals (CQVIP), and Wanfang Database were systematically searched for eligible studies from their inception to March 2021. Thirty-nine randomized controlled trials were involved in this study, and all the data were analyzed by Review Manager 5.3 (Nordic Cochran Centre, Copenhagen, Denmark) and R 4.0.5 software. The meta-analyses suggested that TCMs in combination with capecitabine-based regimens increased objective response rate (ORR) in the palliative treatment of CRC (risk ratio [RR], 1.35 [1.17, 1.55], I2  = 0%), disease control rate (DCR) (RR, 1.22 [1.12, 1.32], I2  = 3%), and quality of life (QOL) (RR, 1.71 [1.44, 2.03], I2  = 0%), with decreased risks of myelosuppression, anemia, thrombocytopenia, liver/renal dysfunction, neurotoxicity, nausea/vomiting, neutropenia, diarrhea, leukopenia, improved the peripheral lymphocyte, reduced the expression of tumor markers, and related factors. Further sensitivity analysis of specific plant-based TCMs found that dangshen, fuling, and gancao had significantly higher contributions to the results of the RR. The results show that capecitabine-based chemotherapy combined with TCM in the treatment of CRC increases the efficiency of ORR and DCR, reduces chemotherapeutic agents-associated adverse reactions, and improves their life quality as compared with chemotherapy alone, but further randomized and large sample of studies are needed.

Development and validation of prognostic models for colon adenocarcinoma based on combined immune-and metabolism-related genes.

Background: The heterogeneity of tumor tissue is one of the reasons for the poor effect of tumor treatment, which is mainly affected by the tumor immune microenvironment and metabolic reprogramming. But more research is needed to find out how the tumor microenvironment (TME) and metabolic features of colon adenocarcinoma (COAD) are related. Methods: We obtained the transcriptomic and clinical data information of COAD patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Consensus clustering analysis was used to identify different molecular subtypes, identify differentially expressed genes (DEGs) associated with immune-and metabolism-related genes (IMRGs) prognosis. Univariate and multivariable Cox regression analysis and Lasso regression analysis were applied to construct the prognostic models based on the IMRG risk score. The correlations between risk scores and TME, immune cell infiltration, and immune checkpoint genes were investigated. Lastly, potential appropriate drugs related to the risk score were screened by drug sensitivity analysis. Results: By consensus clustering analysis, we identified two distinct molecular subtypes. It was also found that the multilayered IMRG subtypes were associated with the patient's clinicopathological characteristics, prognosis, and TME cell infiltration characteristics. Meanwhile, a prognostic model based on the risk score of IMRGs was constructed and its predictive power was verified internally and externally. Clinicopathological analysis and nomogram give it better clinical guidance. The IMRG risk score plays a key role in immune microenvironment infiltration. Patients in the high-risk groups of microsatellite instability (MSI) and tumor mutational burden (TMB) were found to, although with poor prognosis, actively respond to immunotherapy. Furthermore, IMRG risk scores were significantly associated with immune checkpoint gene expression. The potential drug sensitivity study helps come up with and choose a chemotherapy treatment plan. Conclusion: Our comprehensive analysis of IMRG signatures revealed a broad range of regulatory mechanisms affecting the tumor immune microenvironment (TIME), immune landscape, clinicopathological features, and prognosis. And to explore the potential drugs for immunotherapy. It will help to better understand the molecular mechanisms of COAD and provide new directions for disease treatment.

[Effects and safety of varying doses of guizhi fuling capsule in patients with primary dysmenorrhea: a multi-center, randomized, double-blind, placebo-controlled clinical study].

To evaluate the effects and safety of varying doses of Guizhi Fuling capsule on treating primary dysmenorrhea. From August 2010 to March 2011, 240 subjects (aged 18-30) with primary dysmenorrheal, were enrolled in 8 sites. They were randomized into Guizhi Fuling capsule high dose group, low dose group and placebo control group, 80 cases in each group. These patients were treated for three consecutive menstrual cycles, then were followed up in another three consecutive menstrual cycles. Visual analogue scales (VAS) was used to determine the pain intensity. During the treatment, the high-, low-dose and placebo groups efficiency on pain relief are 68.42%, 67.57% and 47.89% respectively. Guzhi Fuling (included high- and low- dose group) significantly relieves the pain compared to placebo. In follow-up, Guzhi Fuling groups are still superior to the placebo group (73.68%, 72.97% and 53.52%). During the treatment, pain duration reduces 57.88% in high dose group, while 46.17% in low dose group, and 30.40% in placebo group. In follow-up, pain lasting time decrease 67.93%, 53.56%, 47.46%, respectively. Guizhi Fuling significantly reduces the pain duration compared to placebo and high-dose is better than low-dose. The efficacy of Guzhi Fuling (high- and low-dose) displays certain dosage-effect relationship. Among these group, no serious adverse event was reported. Guizhi Fuling capsule at high or low dose significantly relieves the pain, improves symptoms, reduces the duration of pain, and has a better overall treatment effect and long-term treatment effect in patients with primary dysmenorrhea.

[Study on the reliability and validity of the Chinese Menopause Rating Scale (CMRS)].

OBJECTIVE: To evaluate the feasibility, reliability, validity and responsiveness of a Chinese Menopause Rating Scale (CMRS). METHODS: Cross-sectional survey and convenience sampling were adopted. PARTICIPANTS: women with menopause syndrome and those in menopause but without menopause syndrome were recruited. All participants were asked to complete the CMRS, Kupperman Index, WHOQOL-BREF and MENQOL. The Self-control observation design was adopted when the responsiveness was evaluated. Patients were treated with TCM for weeks. MRSTCM was evaluated before and after the treatment. RESULTS: (1) Feasibility: 3343 participants including 2320 patients and 1023 menopause women, were surveyed in 8 different settings. The recovery rate of CMRS was 100%, with a response rate as 99.7%. The completion of the CMRS took 10.30 minutes on average. (2)Reliability: Cronbach's alpha of CMRS, soma dimension, psychology dimension and community dimension of CMRS were 0.93, 0.87, 0.89 and 0.73 respectively, with the correlation coefficient of split half of the CMRS. Soma dimension, psychology dimension and community dimension were 0.92, 0.89, 0.86 and 0.73 respectively and the test-retest correlation coefficient of MRSTCM, the soma dimension, psychology dimension and community dimension were as 0.88, 0.91, 0.85 and 0.77 respectively. (3) VALIDITY: CMRS was established on the basis of connotation of menopause syndrome, and a series of steps were adopted to modify the scale. CMRS was applicable for patients with menopause syndrome. CMRS seemed to have had good content-related validity. The result of exploratory factor analysis was accorded with the theory frame of CMRS by and large. The correlations between CMRS and KI, CMRS and WHOQOL-BREF, CMRS and MENQOL seemed good. The CMRS was able to discriminate between groups of people with or without menopausal syndrome and had good discriminative validity. (4) Responsibility: The CMRS was measured based on 174 patients with menopausal syndrome before and after the TCM therapy. Our result showed that the CMRS having the ability to measure the clinically important differences. CONCLUSION: CMRS was suitable for outcome assessment of menopausal syndrome. This primary research proved that the CMRS had good feasibility, reliability, validity as well as responsiveness.

[An algorithm study on telecardiogram diagnosis based on multivariate autoregressive model and two-lead ECG signals].

OBJECTIVE: In view of the time delay caused by reconstruction of signals at remote sites, a direct classification method with high accuracy suitable for telediagnosis of electrocardiogram (ECG) signals is studied. METHOD: The data for analysis and classification was obtained from MIT-BIH database, including 300 samples each of normal sinus rhythm (NSR), atria premature contraction (APC), premature ventricular contraction (PVC), ventricular tachycardia (VT), ventricular fibrillation (VF) and superventricular tachycardia (SVT). An multivariate autoregressive (MAR) model based technique that could combine the signals of two ECG leads was presented to classify the ECGs directly, including MAR modeling performed on ECGs, and quadratic discrimination function (QDF) based classification by using MAR coefficients and K-L MAR coefficients. RESULT: Besides quick and convenient diagnosis, the accuracy of the proposed classification algorithm was as high as 98.3%-100%. CONCLUSION: The MAR modeling based technique is suitable for telecardiogram diagnosis. Comparing with single-lead ECGs, better classification results can be obtained through the combination of two-lead ECG signals.