Background. The practice of traditional Chinese medicine (TCM) began several thousand years ago, and the knowledge of practitioners is recorded in paper and electronic versions of case notes, manuscripts, and books in multiple languages. Developing a method of information extraction (IE) from these sources to generate a cohesive data set would be a great contribution to the medical field. The goal of this study was to perform a systematic review of the status of IE from TCM sources over the last 10years. Methods. We conducted a search of four literature databases for articles published from 2010 to 2021 that focused on the use of natural language processing (NLP) methods to extract information from unstructured TCM text data. Two reviewers and one adjudicator contributed to article search, article selection, data extraction, and synthesis processes. Results. We retrieved 1234 records, 49 of which met our inclusion criteria. We used the articles to (i) assess the key tasks of IE in the TCM domain, (ii) summarize the challenges to extracting information from TCM text data, and (iii) identify effective frameworks, models, and key findings of TCM IE through classification. Conclusions. Our analysis showed that IE from TCM text data has improved over the past decade. However, the extraction of TCM text still faces some challenges involving the lack of gold standard corpora, nonstandardized expressions, and multiple types of relations. In the future, IE work should be promoted by extracting more existing entities and relations, constructing gold standard data sets, and exploring IE methods based on a small amount of labeled data. Furthermore, fine-grained and interpretable IE technologies are necessary for further exploration.

Although persistent hepatitis B virus (HBV) infection is associated with natural killer (NK) cell dysfunction, it remains obscure whether HBV viral antigens are responsible for NK cell dysfunction in patients with chronic hepatitis B (CHB) infection. In this study, we found that the percentage of NK cells expressing the inhibitory receptor, NKG2A, was increased in CHB patients, and NKG2A blockade restored NK cell function. Furthermore, in CHB patients, the frequency of NK cells expressing NKG2A positively correlated with the number of regulatory T cells (Tregs) and production of interleukin-10 (IL-10) in these Tregs. Moreover, exposure of peripheral blood mononuclear cells (PBMCs) isolated from healthy controls to sera from CHB patients resulted in increased proportion of NKG2A⁺ NK cells; IL-10 blockade reduced the frequency of NKG2A⁺ NK cells while increasing the percentage of IFN-γ⁺ NK cells. In addition, stimulation of NK cells and Tregs from healthy controls with CHB sera together with anti-IL-10 antibody increased IFN-γ production in the culture supernatant. The frequencies of NKG2A⁺ NK cells and IL-10⁺ Tregs, along with serum levels of alanine transferase and HBV DNA, were significantly increased in CHB patients positive for the Hepatitis B e antigen (HBeAg, a marker of viral replication) when compared to HBeAg-negative CHB patients. Importantly, exposure of PBMCs from healthy controls to HBeAg resulted in increased IL-10 production but reduced levels of TNF and IFN-γ, and IL-10 blockade rescued the generation of TNF and IFN-γ in this assay. The reduced production of TNF and IFN-γ was also observed in NK cells and Tregs from healthy controls that were stimulated with HBeAg, while IL-10 blockade increased the secretion of these two cytokines. We conclude that HBeAg induces IL-10 production in Tregs, thereby leading to increased expression of NKG2A on NK cells, which contributes to NK cell dysfunction during CHB infection. These data suggest that HBeAg is associated with NK cell dysfunction in CHB.

Background: In this study, we focus on building a fine-grained entity annotation corpus with the corresponding annotation guideline of traditional Chinese medicine (TCM) clinical records. Our aim is to provide a basis for the fine-grained corpus construction of TCM clinical records in future. Methods: We developed a four-step approach that is suitable for the construction of TCM medical records in our corpus. First, we determined the entity types included in this study through sample annotation. Then, we drafted a fine-grained annotation guideline by summarizing the characteristics of the dataset and referring to some existing guidelines. We iteratively updated the guidelines until the inter-annotator agreement (IAA) exceeded a Cohen’s kappa value of 0.9. Comprehensive annotations were performed while keeping the IAA value above 0.9. Results: We annotated the 10,197 clinical records in five rounds. Four entity categories involving 13 entity types were employed. The final fine-grained annotated entity corpus consists of 1104 entities and 67,799 tokens. The final IAAs are 0.936 on average (for three annotators), indicating that the fine-grained entity recognition corpus is of high quality. Conclusions: These results will provide a foundation for future research on corpus construction and named entity recognition tasks in the TCM clinical domain.

Topoisomerase II (topo II), an enzyme essential for cell viability, is present in mammalian cells as the α- and β-isoforms. In human leukemia HL-60/S or HL-60/doxorubicin (DOX)0.05 cells, the levels of topo IIα- or β-protein were similar in either asynchronous exponential or synchronized cultures. Although topo IIα was hypophosphorylated in HL-60/DOX0.05 compared with HL-60/S cells, both overall and site-specific hyperphosphorylation of topo IIβ was apparent in HL-60/DOX0.05 compared with HL-60/S cells. The phosphorylation of topo IIα and not β was enhanced in the S and G₂ + M phases of HL-60/S cells. In contrast, an increase in the phosphorylation of topo IIβ compared with α was apparent in the G₁ and S phases of HL-60/DOX0.05 cells. The cytotoxicity and depletion of topo IIα or β in cells treated with drug for 1 h revealed that mole-for-mole, amsacrine was 2-fold more effective than etoposide in killing HL-60/S or HL-60/DOX0.05 cells and in depleting the β versus α topo II protein. Present results demonstrate that: 1) hyperphosphorylation of topo IIβ in HL-60/DOX0.05 cells may be a compensatory consequence of the hypophosphorylation of topo IIα to maintain normal topo II function during proliferation, and 2) enhanced sensitivity of HL-60/S or HL-60/DOX0.05 cells to amsacrine may be due to the preferential interaction and depletion of topo IIβ.

Background: Infertility is a reproductive disorder caused by multiple causes and is an adverse event of reproductive health for couples in the reproductive period. Women who do not avoid sex for at least 12 months and are not pregnant are said to be infertile. 10% to 20% of infertility is caused by immune factors. At present, there is no unified diagnostic standard for immunological infertility. Clinically, it is considered that abnormal ovulation and reproductive system function of women are excluded, and no obvious pathogenic factors occur; routine examination of male semen is normal, but there is evidence of anti-reproductive immunity, thus causing infertility is immunological infertility. Traditional Chinese medicine (TCM) has a long history of treating infertility and has remarkable curative effect. It plays an important role in the treatment of gynecological and obstetrical diseases in China. The purpose of this study is to evaluate the efficacy and safety of traditional Chinese medicine for the treatment of immune infertility. Method: we searched the literature from following databases: Cochrane Library, PubMed, China Biomedical Literature Database (CB), EMBASE, Chinese Journal of Science and Technology (VIP), China National Knowledge Infrastructure Database (CNKI) and Wanfang Database were searched. All the databases mentioned above will be searched from the start date to the latest version. A manual search of all references to the included trials, published randomized controlled trials (RCTs) whether blind or unblind, any languages and length of follow up were included. Treatments included Chinese medicinal herbs (single or compound). Controlls were placebo and western medicine, or no intervention. Key outcomes will include pregnancy rates, the efficiency of Chinese herbal medicine (at least one negative antibody for infertility), birth rates (the ratio of the number of pregnant women giving birth to their babies normally after herbal treatment to the total number of patients treated), recurrence rate and safety index. Two evaluators independently retrieved and extracted data and import it into Endnote X8. Then they conduct methodological evaluation on the quality of the included studies, and meta-analysis was conducted with RevMan 5.3 and Stata 13.0 software. We will use the Cochrane risk analysis tool to assess the risk of bias. Differences will be resolved by consensus or through the participation of third parties. All analysis will be performed based on the Cochrane Handbook for Systematic Reviews of Interventions. Results: The purpose of this study is to evaluate the efficacy and safety of traditional Chinese herb medicine in the treatment of immune infertility. Conclusion: This meta-analysis can provide evidence for clinicians to help patients make better choices. Trial registration number: INPLASY2020120073.

Objective ： In this paper, we focused on building a fine-grained entity annotation corpus with corresponding annotation guideline of Traditional Chinese Medicine ( TCM ) clinical records, and to provide an effective way to build more corpora of TCM clinical records in the future. Methods: Instead of previous research methods, we proposed four steps approach which is suitable for TCM medical records in our corpus construction work. Firstly, determine the entity types included in this study through sample annotation method; secondly, draft our fine-grained annotation guideline by summarizing the characteristics of the dataset and referring to some existing guidelines; thirdly, update the guideline through iterative annotations way until the inter-annotator agreement (IAA) value exceed 0.9, kappa value was used to measure the IAA; fourthly, comprehensive annotations were performed, if IAA value exceeds 0.9 stably . After above four method steps, we succeeded to construct the fine-grained entity recognition corpus of TCM clinical records. Results: There are 4 entity categories involving 13 entity types being determined finally. The fine-grained annotated entity corpus consists of 1104 entities and 67799 tokens totally. The final IAAs are 0.93, 0.94, 0.94 respectively (between two of the three annotators), the IAA value show the fine-grained entity recognition corpus are of high quality. We constructed a fine-grained annotated guideline and entity recognition corpus of TCM clinical records. Conclusions: The four-step method was of high quality, the corpus constructed in this study was an encouraging example . Based on this approach, more comprehensive corpus about TCM clinical records will be built to support the TCM named entity recognition tasks in future research.