The integration of Traditional Chinese Medicine (TCM) and Western Medicine in a multidisciplinary approach is the future direction for the diagnosis and treatment of Cancer-Related Fatigue (CRF). However, the lack of standard criteria for syndrome differentiation and treatment selection limits the application of TCM in Western and international contexts. Patients with CRF often experience fatigue associated with metabolic and energy balance abnormalities, with thyroid function playing a critical role in the body's energy metabolism and regulation.
To analyze the TCM syndrome characteristics of CRF and explore their correlation with thyroid function levels, providing a reference for the integrated diagnosis and treatment of CRF and mechanism research in both TCM and western medicine.
The study included cancer patients who visited the oncology outpatient and inpatient departments of the China Academy of Chinese Medical Sciences Xiyuan Hospital in 2021. General information of the patients was collected. The Chinese version of the Revised Piper Fatigue Scale (RPFS-CV) was used to assess patients' fatigue. Thyroid function tests, including triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone, anti-thyroid peroxidase antibody (TPO-Ab), and thyroglobulin antibody, were collected on the day of or the day after enrollment. TCM syndrome characteristics of CRF patients were collected through a self-designed CRF TCM Four-Diagnostic Information Form. Spearman's rank correlation analysis was used to explore the correlation between RPFS-CV fatigue scores and thyroid function indicators. Point biserial correlation analysis was used to investigate the correlation between RPFS-CV fatigue scores, thyroid function indicators, and TCM syndrome characteristics of CRF.
A total of 159 CRF patients were included. The most common types of cancer were lung cancer (50 cases, 31.4%), breast cancer (23 cases, 14.5%), head and neck tumors (21 cases, 13.2%), rectal cancer (21 cases, 13.2%), and colon cancer (18 cases, 11.3%). The median diagnosis duration was 2.15 (3.16) years; 88 patients (55.3%) experienced recurrence or metastasis, with 40 patients (45.5%) having local recurrence and 38 patients (43.2%) having oligometastasis. The median duration of metastasis was 1.50 (2.83) years; 91 patients (57.2%) were in advanced stages, 101 patients (63.5%) had received antitumor treatment, and 57 patients (35.8%) had undergone chemotherapy. In TCM syndromes, deficiency syndromes with a frequency over 10% were Qi deficiency, heart deficiency, and spleen deficiency; among excess syndromes, those occurring more than 20 times were Qi stagnation and damp-cold. Syndromes with a median RPFS-CV fatigue score over 4 were, in descending order, damp-cold, Qi stagnation, spleen deficiency, heart deficiency, liver deficiency, damp-heat, and Qi deficiency. RPFS-CV fatigue scores were positively correlated with Qi deficiency, spleen deficiency, heart deficiency, liver deficiency, damp-cold, and Qi stagnation (P<0.05). RPFS-CV fatigue scores were negatively correlated with FT3 and T3 (P<0.05). Qi deficiency was positively correlated with T4, Kidney deficiency with TPO-Ab, and Qi stagnation with FT4 (P<0.05) ; Damp-heat was negatively correlated with T3 and T4 (P<0.05) .
The fatigue condition of CRF patients is closely related to TCM syndrome characteristics and thyroid function levels. Further research will help deepen the understanding of these correlations and promote the collaborative development of TCM and western medicine in the management of CRF disease.
Traditional Chinese Medicine (TCM) has a systematic understanding of the occurrence, development, diagnosis and treatment of Hashimoto's thyroiditis complicated with thyrotoxicosis. However, at present, there are few studies on the clinical symptoms and syndrome distribution of TCM in this disease population, and there is also a lack of description of the syndrome distribution and syndrome diagnostic criteria of this disease in the national industry standards.
Using factor analysis combine with cluster analysis to explore the distribution of clinical symptoms and syndromes of Hashimoto's thyroiditis complicated with thyrotoxicosis, provide a basis for clinical syndrome differentiation and promote the standardization of Hashimoto's thyroiditis complicated with thyrotoxicosis syndrome.
From December 2020 to December 2021, 171 patients with Hashimoto's thyroiditis complicated with thyrotoxicosis who met the diagnostic criteria in the outpatient department of thyroid disease of Dongcheng District, Tongzhou District of Dongzhimen Hospital, Beijing University of Chinese Medicine and Sunsimiao Hospital was collected. The symptoms, signs, tongue, pulse and other four diagnostic information were collected by using the four diagnostic information collection table of Hashimoto's thyroiditis complicated with thyrotoxicosis'. Based on factor analysis and cluster analysis, the symptoms and syndrome distribution of Hashimoto's thyroiditis complicated with thyrotoxicosis were studied.
Among the 171 patients with Hashimoto's thyroiditis complicated with thyrotoxicosis, there were 17 males and 154 females, with an average age of (39.98±13.30) years. Patients aged 20-60 years accounted for 87.72%. The symptoms with high frequency in the distribution of symptoms were fatigue, palpitation, irritability or impatience. Signs were swelling of the neck, finger tremor. The tongue image with higher frequency had red, thin tongue and tooth marks on the tongue. The moss were white and thin. The pulse condition were pulse string and pulse number. Factor analysis of 82 four diagnostic items of the questionnaire was collected, and 25 common factors were extracted. The cumulative variance contribution rate was 70.562%, and 62 meaningful symptoms were screened out. The 25 common factor results obtained by factor analysis were used as variables to perform R-type system cluster analysis, and a total of 5 types of syndrome types were obtained, namely: pattern of phlegm congealing due to liver depression, pattern of yin deficiency with effulgent fire, pattern of yang deficiency in spleen and kidney, pattern of qi stagnation due to liver depression, pattern of dual deficiency of qi and nutrient phases.
The basic TCM syndromes of Hashimoto's thyroiditis complicated with thyrotoxicosis can be divided into pattern of phlegm congealing due to liver depression, pattern of yin deficiency with effulgent fire, pattern of yang deficiency in spleen and kidney, pattern of qi stagnation due to liver depression, pattern of dual deficiency of qi and nutrient phases.
Thyroid autoantibody is a marker for the diagnosis of Hashimoto's thyroiditis (HT), and B cells are essential in the pathogenesis of HT. Enhancer of Zeste homolog 2 (EZH2), which is an important epigenetic regulator, plays an important role in the regulation of lymphocytes development and function.
To investigate EZH2 expression in plasmoblasts and plasma cells in HT, and further explore the therapeutic effect of EZH2 inhibitors in experimental autoimmune thyroiditis (EAT) model.
The thyroid tissues from 6 patients who underwent thyroidectomy (3 HT patients with PTC, 3 patients with PTC alone) in Peking University First Hospital between 2010 and 2020 were obtained from the contralateral lobe with thyroid cancer, and screened for the expression of B-lymphocyte-related genes by RNA-seq; thyroid tissues from 16 HT patients and 8 normal thyroid tissues were collected and verified for the the expression of EZH2 in B cells in HT thyroid tissues by immunohistochemistry or immunofluorescence, respectively. Fine-needle aspiration (FNA) samples from patients with HT (n=25), and peripheral blood from patients with HT (n=19) or healthy donors (n=12) were analyzed by flow cytometry to define altered EZH2 expression in plasmablasts and plasma cells. Fifteen seven-week-old NOD.H-2h4 mice were randomly divided into the control (n=5), EAT without injection group (n=5), and EZH2 inhibitor+ GSK126 injection group (10 mg/kg, intraperitoneal injection 3 times /week, n=5). The degree of thyroid inflammation and changes in TgAb levels were observed after 8 weeks.
RNA sequencing analysis showed that EZH2 and genes associated with the B-cell phenotype such as CD19, CD27, CD38, CD52 were higher expressed in HT hyroid tissues compared with normal thyroid tissues. Immunohistochemical results showed that immunohistochemical staining for EZH2 in 16 HT thyroid tissue specimens was strongly positive with positive cells observed in the GC region, and no positive cells were observed in the staining of 8 normal thyroid tissues. EZH2 staining in HT thyroid tissue was highly expressed in the GC region, and EZH2 was specifically expressed in CD19+ B cells. The results of flow cytometry assay showed that the proportion of CD19+ B cells, plasmablasts and plasma cells in HT FNA samples was higher than that of HD peripheral blood and HT peripheral blood samples (P<0.01), and the proportion of EZH2 positivity in CD19+ B cells and plasma cells was higher in HT FNA samples than that of HT peripheral blood (P<0.005). In the mouse experiments, lymphocytic infiltration of the thyroid tissues was increased in the EAT group compared to the control group. In the GSK126 treatment groups, the thyroid inflammatory score and serum TgAb titer were significantly higher than the control group and lower than the EAT group.
EZH2 over-expression in CD19+ B cells of HT hyroid tissues may promote the differentiation of B cells into plasma cells and auto-antibody production, which leads to the destruction of thyroid tissues. EZH2 inhibitors can slow down the degree of thyroid inflammation in the EAT model. Increased EZH2 expression in plasmablasts may be involved in the pathogenesis of HT. EZH2 may serve as a therapeutic target for HT, although further studies are needed.
