Treatment of malignant tumors encompasses multidisciplinary comprehensive diagnosis and treatment and reasonable combination and arrangement of multidisciplinary treatment, which is not a simple superimposition of multiple treatment methods, but a comprehensive consideration of the characteristics and specific conditions of the patients and the tumor. The mechanism of tumor elimination by restoring the body’s immune ability is consistent with the concept of “nourishing positive accumulation and eliminating cancer by itself” in traditional Chinese medicine (TCM). The formation and dynamic changes in the tumor microenvironment (TME) involve many different types of cells and multiple signaling pathways. Those changes are similar to the multitarget and bidirectional regulation of immunity by TCM. Discussing the relationship and mutual influence of TCM and antitumor therapy on the TME is a current research hotspot. TCM has been applied in the treatment of more than 70% of cancer patients in China. Data have shown that TCM can significantly enhance the sensitivity to chemotherapeutic drugs, enhance tumor-suppressing effects, and significantly improve cancer-related fatigue, bone marrow suppression, and other adverse reactions. TCM treatments include the application of Chinese medicine monomers, extracts, classic traditional compound prescriptions, listed compound drugs, self-made compound prescriptions, as well as acupuncture and moxibustion. Studies have shown that the TCM functional mechanism related to the positive regulation of cytotoxic T cells, natural killer cells, dendritic cells, and interleukin-12, while negatively regulating of regulatory T cells, tumor-associated macrophages, myeloid-derived suppressive cells, PD-1/PD-L1, and other immune regulatory factors. However, the application of TCM in cancer therapy needs further study and confirmation. This article summarizes the existing research on the molecular mechanism of TCM regulation of the TME and provides a theoretical basis for further screening of the predominant population. Moreover, it predicts the effects of the combination of TCM and antitumor therapy and proposes further developments in clinical practice to optimize the combined strategy.

BackgroundThere is a crosstalk between gut microbiota (GM) and cancer immunotherapy (CI). The purpose of this study is to use bibliometric analysis to identify the highly cited papers relating to GM/CI and explore the research status and development trends of the GM/CI research.MethodsA literature search regarding GM/CI publications from 2012 to 2021 was undertaken on July 4, 2022. The article titles, journals, authors, institutions, countries, total citations, keywords, and other information were extracted from the Science Citation Index Expanded (SCIE) of Web of Science Core Collection (WoSCC). The Bibliometrix of R package and VOSviewer were used for bibliometric analysis.ResultsA total of 665 papers were extracted. The number of papers has increased rapidly over the past decade, especially after 2018. The United States and China had the most publications and made great contributions to this field. Th5e Univ Texas MD Anderson Canc Ctr and Univ Paris Saclay were absolutely in the leading position in GM/CI. The most influential authors were Zitvogel L and Routy B. Frontiers in Immunology had the most publications and Science had the most total citations. Historical direct citation analysis explained the historical evolution in GM/CI. Highly cited papers and high-frequency keywords illustrated the current status and trends of GM/CI. Four clusters were identified and the important topics included the role of GM and antibiotics in CI, the methods of targeting GM to improve CI outcomes, the mechanism by which GM affects CI and the application of ICIs in melanoma. “Tumor microbiome”, “proton pump inhibitors” and “prognosis” may be the new focus of attention in the next few years.ConclusionThis study filtered global publications on GM/CI correlation and analyzed their bibliometric characteristics, identified the most cited papers in GM/CI, and gained insight into the status, hotspots and trends of global GM/CI research, which may inform researchers and practitioners of future directions.

Background: Alternative splicing (AS) is a molecular event that drives protein diversity through the generation of multiple mRNA isoforms. Growing evidence demonstrates that dysregulation of AS is associated with tumorigenesis. However, an integrated analysis in identifying the AS biomarkers attributed to esophageal carcinoma (ESCA) is largely unexplored. Methods: AS percent-splice-in (PSI) data were obtained from the TCGA SpliceSeq database. Univariate and multivariate Cox regression analysis was successively performed to identify the overall survival (OS)-associated AS events, followed by the construction of AS predictor through different splicing patterns. Then, a nomogram that combines the final AS predictor and clinicopathological characteristics was established. Finally, a splicing regulatory network was created according to the correlation between the AS events and the splicing factors (SF). Results: We identified a total of 2389 AS events with the potential to be used as prognostic markers that are associated with the OS of ESCA patients. Based on splicing patterns, we then built eight AS predictors that are highly capable in distinguishing highand low-risk patients, and in predicting ESCA prognosis. Notably, the area under curve (AUC) value for the exon skip (ES) prognostic predictor was shown to reach a score of 0.885, indicating that ES has the highest prediction strength in predicting ESCA prognosis. In addition, a nomogram that comprises the pathological stage and risk group was shown to be highly efficient in predicting the survival possibility of ESCA patients. Lastly, the splicing correlation network analysis revealed the opposite roles of splicing factors (SFs) in ESCA. Conclusion: In this study, the AS events may provide reliable biomarkers for the prognosis of ESCA. The splicing correlation networks could provide new insights in the identification of potential regulatory mechanisms during the ESCA development.

Background. Malignant pleural effusion (MPE) is a common complication in most malignancies. Despite its frequent occurrence, current knowledge of MPE remains limited and the effect of the management is still unsatisfying. Traditional Chinese medicine (TCM) external treatment has unique advantages, such as quicker efficacy and fewer side effects. Objective. To observe the effects and safety of Kang’ai Xiaoshui ointment (TCM herbal ointment) in MPE. Design. This was a placebo-controlled double-blinded randomized study. A total of 80 patients were enrolled, of which 72 were randomized to receive Kang’ai Xiaoshui ointment or placebo at an allocation ratio of 1:1. Kang’ai Xiaoshui ointment or placebo was applied on the thorax wall for 8 hours daily. The intervention lasted 2 weeks. Kang’ai Xiaoshui ointment consisted of Astragalus membranaces （黄芪）, Semen pharbitidis （牵牛子）, Cassia twig （桂枝）, Pericarpium arecae （大腹皮）, Curcuma zedoary （莪术）, Borneol （冰片), and other substances. In both groups, diuresis and drainages were used as needed. Outcomes covered the quantity of pleural effusion evaluation, TCM Symptom Scale, Karnofsky Performance Scale, and safety indicators such as routine blood test, blood biochemistry test, and response table of skin irritation. Results. Of 72 patients randomized to receive Kang’ai Xiaoshui ointment or placebo along with symptomatic treatment, the response rate was documented as 42.4% for the treatment group and 25.0% for the placebo group (P = .138). As for the TCM symptom scale, the treatment group showed improvement in chest distress (P = .003), fullness and distention (P = .042), shortness of breath (P < .001), no statistical significance in palpitation (P = .237), and pain (P = .063), whereas the placebo group did not show statistical significance in any of the 5 symptoms. Major adverse events related to the treatment, mainly skin irritation, were distributed equally. Conclusions. Kang’ai Xiaoshui ointment showed a potential of reducing MPE, and it could alleviate symptoms of dyspnea. Thus, it may be appropriate as a supplementary intervention for MPE. There were some flaws in the study design. A larger scale and better designed trial is advocated.

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