A New Method for Syndrome Classification of Non-Small-Cell Lung Cancer Based on Data of Tongue and Pulse with Machine Learning.

OBJECTIVE: To explore the data characteristics of tongue and pulse of non-small-cell lung cancer with Qi deficiency syndrome and Yin deficiency syndrome, establish syndrome classification model based on data of tongue and pulse by using machine learning methods, and evaluate the feasibility of syndrome classification based on data of tongue and pulse. METHODS: We collected tongue and pulse of non-small-cell lung cancer patients with Qi deficiency syndrome (n = 163), patients with Yin deficiency syndrome (n = 174), and healthy controls (n = 185) using intelligent tongue diagnosis analysis instrument and pulse diagnosis analysis instrument, respectively. We described the characteristics and examined the correlation of data of tongue and pulse. Four machine learning methods, namely, random forest, logistic regression, support vector machine, and neural network, were used to establish the classification models based on symptom, tongue and pulse, and symptom and tongue and pulse, respectively. RESULTS: Significant difference indices of tongue diagnosis between Qi deficiency syndrome and Yin deficiency syndrome were TB-a, TB-S, TB-Cr, TC-a, TC-S, TC-Cr, perAll, and the tongue coating texture indices including TC-CON, TC-ASM, TC-MEAN, and TC-ENT. Significant difference indices of pulse diagnosis were t4 and t5. The classification performance of each model based on different datasets was as follows: tongue and pulse < symptom < symptom and tongue and pulse. The neural network model had a better classification performance for symptom and tongue and pulse datasets, with an area under the ROC curves and accuracy rate which were 0.9401 and 0.8806. CONCLUSIONS: It was feasible to use tongue data and pulse data as one of the objective diagnostic basis in Qi deficiency syndrome and Yin deficiency syndrome of non-small-cell lung cancer.

Bone marrow angiogenesis in patients presenting with differential Chinese medicine syndrome: correlation with the clinico-pathological features of aplastic anemia.

OBJECTIVE: To explore differences in bone marrow angiogenesis seen in aplastic anemia (AA) patients presenting with differential Chinese medicine (CM) syndrome, and to correlate these differences with clinical pathology. METHODS: Thirty-five patients were enrolled, including 18 with "yang deficiency syndrome" and 17 with "yin deficiency syndrome." Bone marrow biopsies and serum were collected. Microvessel density (MVD) and positive expression of vascular endothelial-derived growth factor (VEGF) were detected by immunohistochemisty. Hypoxia inducible factor -1α (HIF-1α), and VEGF expression were assayed by enzyme-linked immunoabsorbent assay (ELISA), serum lactate dehydrogenase (LDH) was tested by enzyme method and liquid chip technology was used to detected the expression of interleukin (IL)-2, IL-4, IL-6, IL-10, interferon (IFN)-γ and tumor necrosis factor (TNF)-α. RESULTS: Counts for leukocytes, absolute neutrophils and platelets in "yin deficiency syndrome" were lower than those found in "yang deficiency syndrome" (P<0.05). MVD and VEGF expression, and the positive rate of CD34 and VEGF in bone marrow were lower in AA, especially in "yin deficiency syndrome" (P<0.01 or P<0.05). "Yin deficiency syndrome" displayed decreased VEGF and LDH expression, and enhanced expression of HIF-1α as compared to "yang deficiency syndrome" (P<0.05). Levels of IL-4 and IL-6 were higher in AA (P<0.01), but IL-10 was decreased (P<0.05). High TNF-α expression was seen in "yang deficiency syndrome" and IFN-γ expression was decreased in "yin deficiency syndrome" as compared with normals (P <0.01 and P<0.05, respectively). CONCLUSION: AA patients have lower MVD than normals, especially in "yin deficiency syndrome." MVD might differentially correlate to disease severity, and could be dependent on bone marrow or serum VEGF expression and LDH. Additionally, IL-2, IL-10, IL-4 and IFN-γ were negatively associated while IL-6 and TNF-α were positively associated with MVD.

[Analysis of associated rules between Chinese medical syndrome typing features of epigastric pain and endoscopic features].

OBJECTIVE: To explore Chinese medical syndrome typing features of epigastric pain and its association with gastroscopic manifestations. METHODS: Using associated rules data mining method, an analysis study was performed in 234 patients with epigastric pain by combining holistic Chinese medical syndrome typing and results of gastroscopic examinations. RESULTS: Pi-Wei deficiency cold syndrome (PWDCS) was associated with pale gastric mucosa, or superficial ulcers accompained with unobvious redness and swelling. Inversed Gan-qi invading Wei syndrome (IGIWS) was associated with bile regurgitation. Damp-heat stagnating in the middle jiao syndrome (DSMJS) was associated with obvious redness and swollen mucosa, or ulcers accompanied with yellow and white fur. Wei-yin exhaustion syndrome (WYES) was associated with coarse mucosa and exposed blood vessels, or rare mucus. Retention of blood stasis in Wei syndrome was associated with bulged swelling and erosion. Indigestion impairing Wei syndrome (IIWS) was associated with retention of water and food, or more mucus attached. The endoscopic manifestations of PWDCS and DSMJS occurred most frequently, while PWDCS and IGIWS ranked the first place in macroscopic Chinese medical syndrome typing. CONCLUSIONS: The manifestations of endoscopic features were closely associated with Chinese medical syndrome typing. The syndrome typing features of epigastric pain could be objectively and further grasped by summarizing syndrome typing laws using modern devices such as gastroscopic examinations, thus improving the accuracy of clinical syndrome typing.

Comfortable lifestyle-induced imbalance of neuro-endocrine-immunity network: a possible mechanism of vascular endothelial dysfunction.

OBJECTIVE: To observe the changes of vascular endothelial functions and general neuro-endocrine-immunity (NEI) network under the state of qi-deficiency syndrome induced by excessive idleness and to approach their internal relevance and illuminate initially the pathophysiological mechanism of vascular lesion induced by excessive idleness. METHODS: A total of 100 male Wistar rats were randomly divided into the control group and the qi-deficiency syndrome model group, 50 rats in each group. The qi-deficiency syndrome model was established by feeding the animals with hyper-alimentation diet in combination with restricting movement for 10 weeks. Changes of common chemical signal molecules related to NEI and vascular endothelial functions were measured by the end of the experiment. Furthermore, their internal relevance was analyzed by the method of canonical correlation analysis. RESULTS: The vascular endothelial structure and function were obviously injured in the model group. Compared with the control group, the chemical signal molecules, such as 5-hydroxytryptamine (5-HT), corticosterone (CORT), triiodothyronine (T3), tetraiodothyronine (T4), angiotensin II (Ang II), interleukin-1 (IL-1), and tumor necrosis factor-alpha (TNF-alpha) in peripheral blood of the model group (n=43) were changed significantly (P<0.05 or P<0.01). Canonical correlation analysis showed that vascular endothelial dysfunction was correlated to the changes of these signal molecules in the NEI network. CONCLUSIONS: Comfort-based lifestyle induced not only vascular endothelial dysfunction but also an imbalance of the NEI network. Vascular endothelial dysfunction and the imbalanced NEI network interacted with each other, and an imbalance of the NEI network may be the pathophysiologic basis for the genesis and development of vascular endothelial dysfunction, even diseases of the blood vessel.

Relationship between various Chinese medicine types and T-cell subsets in patients with ulcerative colitis.

OBJECTIVE: To investigate the relationship between various Chinese medicine (CM) types and T-cell subsets (CD4(+) and CD8(+)) in the colonic mucous membranes of patients with ulcerative colitis (UC). METHODS: Fifty UC patients were enrolled, after differentiation into four types by CM syndromes, i.e., the internal heat-damp accumulation type (IHDA), the qi-stagnancy with blood stasis type (QSBS), the Pi-Shen yang-deficiency type (PSYD) and the yin-blood deficiency type (YBD). From every patient, 3-5 pieces of intestinal mucous membrane tissues were taken through colonoscopy to determine the levels of the T-cell subsets (CD4(+) and CD8(+)) using immunohistochemical method. The results were compared with those in the normal control. RESULTS: The level of CD8(+)increased and the ratio of CD4(+)/CD8(+)decreased mainly in colonic mucous membranous tissues in UC patients. The level of CD4(+)decreased significantly in IHDA types (P<0.01), but decreased only slightly in the PSYD, QSBS and YBD types. CD8(+)increased significantly in the IHDA types (P<0.01), but only slightly in the other three types. CONCLUSION: The IHDA types of UC are closely related with T-cell subsets. The difference of T-cell subsets in various IHDA types of UC patients has provided a theoretical basis for syndrome differentiation in the CM typing of UC.

[Observation on effects of Zhiling Capsule in treating 400 patients with various types of cancer in mid-ad-vanced stage].

OBJECTIVE: To observe the efficacy of Zhiling Capsule (ZLC) in improving symptoms and quality of life (QOL) in patients with various types of cancer in mid-advanced stage. METHODS: A multi-centre randomized and controlled trial was conducted. Four hundred patients with mid-advanced cancer were assigned to two groups: the treatment group (300 cases) treated with ZLC and the control group (100 cases) with Pingxiao Capsule (PXC), both were given orally for two weeks. Clinical symptoms, QOL, weight and adverse reactions were observed before and after treatment. RESULTS: Improving rate of symptom, increasing rates of QOL and weight in the treatment group were all higher than those in the control group (P<0.05); and no obvious adverse reaction was observed in the two groups. CONCLUSION: ZLC could alleviate the qi-yin deficiency syndrome and pain syndrome and improve QOL in patients with various types of cancer in mid-advanced stage.

[Study on correlation between TCM syndrome type and pathological changes of liver tissue in 260 patients with chronic hepatitis B].

OBJECTIVE: To study the correlation between TCM syndrome type and liver tissue pathological changes in patients with chronic hepatitis B (CHB) in order to provide evidence for syndrome differentiation. METHODS: Syndrome typing as well as liver pathological grading and staging of liver biopsy were performed on 260 patients with CHB, then the relationship between them was analyzed. RESULTS: (1) The grade of liver inflammation was mainly G1 and G2 in patients of Gan-qi stagnation and Pi-deficiency type (type 1); G2 in patients of inner damp-heat retention type (type II); G3 in patients of Gan-Shen yin-deficiency type (type lII) and Pi-Shen yang-deficiency type (type IV); while G4 occurred mainly in patients of blood stasis blocking collateral type (type V), showing significant difference as compared with other syndrome types. (2) The liver pathological stage in patients of type I and II was mainly S1 and S2, while S3 and S4 occurred mainly in patients of type III and type IV. (3) The pathological change was mainly G3-G4 and S3-S4 in blood stasis syndrome, while it was mainly G1-G2 and S1-S2 in non-blood stasis syndrome. CONCLUSION: The TCM syndrome type is correlated with liver tissue pathological change to certain extent, among them, syndrome with or without blood stasis showed the closest correlation. The syndrome type of CHB patients developed, along with the aggravating of liver pathological injury, from sthenia to asthenia, from qi to blood, and finally to the blood stasis blocking collateral. So the treatment should be lay stress on activating blood circulation to remove stasis, and be implemented by 3 stages.

[Effects of Eupolyphaga Sinensis Walker on erythrocyte's CR1 activity and anti-cardiolipin antibody level in rats with stagnation of blood].

AIM: To study the effect of Eupolyphaga Sinensis Walker(ESW) on red blood cell immune adherence (RCIA) and serum anticardiolipin antibody level in rat model of Yin-deficiency Huo-excess with chronic blood stasis. METHODS: The model was made by i.m. injection of dexamethasone (0.5 mg/kg) and adrenaline (0.84 mg/kg). The serum anti-cardiolipin antibodies (ACA) ACA-IgG, ACA-IgA and ACA-IgM and the plasma D-dimmer levels were measured by using enzyme-linked immunosorbent assay (ELISA). The body and organ weight of the rats were measured. RESULTS: For rats of Yin-deficiency Huo-excess, rosette rates of red blood cell C3b receptors (RBC-C3b RR) and red blood cell cancer (RBC-CaR) decreased, the serum ACA-IgG, ACA-IgA, ACA-IgM and the plasma D-dimmer levels markedly increased, body weight and the weight of spleen and thymus all decreased. ESW (5 mg/kg, 10 mg/kg) increased RBC-C3bRR and RBC-CaR, reduced serum ACA-IgG, ACA-IgA, ACA-IgM and plasma D-dimmer levels, and increased spleen weight of the rats. CONCLUSION: ESW can boost the immune function in rats of Yin-deficiency Huo-excess with chronic blood stasis.

[Relationship of plasma endotoxin level with TCM deficiency/excess syndrome and grading/staging of pathologic change of liver in patients with chronic hepatitis].

OBJECTIVE: To explore the relationship of plasma endotoxin level with TCM deficiency/excess Syndrome and the grading/staging of pathologic change of liver in patients with chronic hepatitis B (CHB). METHODS: Plasma level of endotoxin (ET) was determined using chromogenic limulus amebocyte lysate (LAL) assay in 75 patients with chronic hepatitis B (30 of excess dominance, 45 of deficiency dominance) and also in 15 healthy subjects for control. Moreover, pathological examination on liver biopsy of 20 patients was conducted. RESULTS: (1) ET level increased in all CHB patients, and the increment was higher in patients of excess dominance than that in patients of deficiency dominance, showing significant difference (P < 0.01). (2) Correlation between ET level and liver pathological grading/staging was shown in CHB patients. CONCLUSION: Plasma level of ET could be taken as one of the criteria of TCM microcosmic diagnosis in differentiating deficiency/excess syndrome. (2) Endotoxemia plays an important role in pathologic process of liver injury.

[Preliminary study on relationship between syndrome differentiation of esophageal cancer and changes of exfoliated cells of tongue coating].

Exfoliated cells of tongue coating of 63 esophageal cancer (EC) cases have been investigated by applying exfoliate cytologic examination, which showed that abnormal cornified cells were commonly seen while they were less in the patients of EC than those in the healthy group, and their difference was significant (P < 0.05), It showed an increase mainly in the number of pro-cornified cells in the patient of the Qi-Yang Deficiency group, an increase mainly in completely cornified cells in the Yin Deficiency and an increase in both pro-cornified cells and completely cornified cells in Phlegn-Dampness and blood Stasis patients. The difference among four groups was significant (P < 0.05). The changes of exfoliated cells of tongue coating provided an objective index for the early diagnosis of EC.

Comparative observations on the types of atrophic gastritis and biopsy pathology of gastric mucosa.

300 cases of chronic atrophic gastritis were classified into 3 types of qi-deficiency of spleen and stomach, yang-deficiency of spleen and stomach, and yin-deficiency of spleen and stomach according to syndrome differentiation of traditional Chinese medicine. The biopsy specimens of gastric mucosa were examined histopathologically and for the presence of pyloric spirobacteria. The results showed that the type of yin-deficiency was the most serious in the degree of pathologic changes, or the glandular atrophy and the interstitial inflammatory cellular infiltration, while the rate of pyloric spirobacteria presence was comparable in all types.

[Pathomorphologic changes on 150 chronic atrophic gastritis patients by treatment based on syndrome differentiation].

Xiang-sha Warming (XSW) and Shashen Nourishing Decoction (SSN) were used in treating Yang Deficiency Syndrome (YaDS) and Yin Deficiency Syndrome (YiDS) of chronic atrophic gastritis (CAG) respectively. 121 cases with Spleen YaDS, and 29 cases with Spleen YiDS were selected. 26 and 30 specimens were taken from gastric mucosa for observation under the SEM and TEM, including 12 and 12 YaDS cases, 14 and 12 Spleen Qi Deficiency cases respectively, 2 cases of YiDS were also observed with TEM. The specimens were taken from the same site of the gastric mucosa directly under the gastroscope pre- and post-treatment. 43 patients (35.6%) with spleen YaDS and 5 cases (17.2%) in Spleen YiDS showed marked effect after 3-month treatment. It showed that the effect in Spleen YaDS was better than YiDS. The XSW was superior than that of SSN. The effects were related to the syndromes and the degrees of pathologic change. This showed that the recipe could somewhat reverse and restore the abnormal glands of gastric mucosa.

[Pathology of syndrome-differentiation types of superficial deficiencies in patients with gastric cancer].

Analysing the relations between TCM syndrome differentiation type and pathology in 312 patients with gastric cancer, the authors put forward the syndrome differentiation type of deficiency of vitality and excess in superficiality. The studies showed that the four syndrome types of deficiency of vitality such as Spleen-Stomach deficiency, Qi-Xue deficiency, Yin deficiency and inner heat, Spleen-Kidney Yang deficiency and the three syndrome types of excess in superficiality such as Liver-Stomach disorder, blood stasis and stagnation of Qi, Phlegm-dampness and stagnation of toxic. The same changes in pathologic characteristic of both were from early to late stage, the infiltration getting deeper, the tumor getting larger and the metastasis of lymph nodes around the stomach from little to much. Their difference was that in the deficiency of vitality syndrome-type, the chief manifestation was in nest or spread infiltration type which became serious by degrees, whereas in excess in superficiality type, the reaction of lymphoidocytes around the cancer was decreasing. The studies also showed that in most syndrome types of Spleen-Kidney Yang deficiency and Phlegm-dampness and stagnation of toxic, the tumor occurred in wide-range and the degree of tissue differentiation was quite low. The authors suggested that there might be morphopathologic basis in TCM syndrome differentiation types and the conclusion has practical value in guiding clinics.