The Efficacy of Long-Term Chinese Herbal Medicine Use on Lung Cancer Survival Time: A Retrospective Two-Center Cohort Study with Propensity Score Matching.

OBJECTIVE: To explore the efficacy of long-term use of Chinese herbal medicine (CHM) on survival time of lung cancer. METHODS: We conducted a retrospective cohort study on lung cancer patients. A propensity score matching (PSM) was performed to balance the covariates. Progression-free survival (PFS) was the primary endpoint and overall survival (OS) was the secondary endpoint. Patients who received CHM therapy from the initial date of diagnosis of lung cancer were included in the CHM group. Patients who were not treated with CHM during the same interval were categorized in the control group. A Cox regression model was used to explore the prognostic factors related to lung cancer. Hazard ratios of different subgroups were also analyzed. RESULTS: A total of 1134 patients were included in our study: 761 patients were in the CHM group and 373 patients were in the control group. After PSM, the mPFS and mOS in the CHM group were 70.4 months and 129.1 months, respectively, while the mPFS and mOS in the control group were 23.8 months and 99.7 months, respectively. The results of survival analysis on each stage demonstrated that patients may benefit from the long-term CHM treatment especially for patients with early stage. One-year to ten-year progression-free survival rates in the CHM group were higher than those in the control group (p < 0.001). COX multivariate regression analysis indicated that CHM treatment, female, low age at diagnosis, early tumor stage, and surgery were independent protective factors against recurrence and metastasis of lung cancer. Subgroup analysis showed that CHM treatment could reduce the risk of recurrence and metastasis in each subgroup (p < 0.01). CONCLUSION: Long-term CHM treatment with the Fuzheng Quxie Formula, which can be flexibly applied in the course of lung cancer treatment, not only has a positive influence on the progression-free survival time of lung cancer patients, but also reduces the risk of recurrence and metastasis of lung cancer.

Combining triptolide with ABT-199 is effective against acute myeloid leukemia through reciprocal regulation of Bcl-2 family proteins and activation of the intrinsic apoptotic pathway.

Bcl-2 inhibitors display an effective activity in acute myeloid leukemia (AML), but its clinical efficacy as a monotherapy was limited in part owing to failure to target other antiapoptotic Bcl-2 family proteins, such as Mcl-1. In this context, the combination strategy may be a promising approach to overcome this barrier. Here, we report the preclinical efficacy of a novel strategy combining ABT-199 with triptolide (TPL), a natural product extracted from a traditional Chinese medicine, in AML. Combination treatment exhibited markedly increased cytotoxicity in leukemic cells irrespective of p53 status while largely sparing normal cells of the hematopoietic lineage. Moreover, co-administration of ABT-199 with TPL dramatically suppressed leukemia progression as well as prolonged animal survival in a xenograft AML model. The potentiated effect of ABT-199 and TPL against AML was associated with activation of the mitochondrum-related intrinsic apoptotic pathway through a mechanism reciprocally modulating Bcl-2 family proteins. In this case, TPL not only downregulated Mcl-1 but also upregulated proapoptotic BH3-only proteins, thereby overcoming the resistance toward ABT-199. Conversely, ABT-199 abrogated Bcl-2-mediated cytoprotection against TPL. Together, these findings suggest that the regimen combining TPL and ABT-199 might be active against AML by inducing robust apoptosis through reciprocal regulation of anti- and proapoptotic Bcl-2 family proteins, therefore providing a strong rationale for the clinical investigation of this combination regimen for the treatment of AML.

[Effects of Jianpi Huoxue Decoction on Kupffer cell signal pathway activation in rats with liver injury induced by Lieber-Decarli liquid diet and lipopolysaccharide].

OBJECTIVE: To observe the effects of Jianpi Huoxue Decoction, a compound Chinese herbal medicine, on Kupffer cell signal pathway activation in rats with liver injury induced by Lieber-Decarli liquid diet and lipopolysaccharide (LPS). METHODS: SD rats were divided into normal, control liquid diet, ethanol liquid diet and ethanol liquid diet plus Jianpi Huoxue Decoction group. Rats were administrated with Jianpi Huoxue Decoction or distilled water via gastrogavage for 4 weeks after administration with ethanol or control liquid diet for 2 weeks respectively. After that, rats in each group were stimulated with LPS via gastrogavage for 3.5 h and harvested. Alanine aminotransferase (ALT) in serum and triglyceride (TG) in liver were analyzed. Pathological changes in liver tissues were observed in HE staining section. Tumor necrosis factor-alpha(TNF-alpha) in portal vein plasma was assayed by ELISA. The protein expressions of CD68, Toll-like receptor 4 (TLR4), phosphorylation-I kappa B (P-I kappa B) and TNF-alpha in liver were evaluated with Western-blotting. RESULTS: After the treatment with Jianpi Huoxue Decoction, the pathologic changes in liver tissue were lightened, levels of ALT in serum, TG in liver and TNF-alpha in portal vein plasma were decreased, and the protein expressions of CD68, TLR4, P-IkappaB and TNF-alpha in liver were reduced. CONCLUSION: Jianpi Huoxue Decoction can inhibit Kupffer cell signal pathway activation in rats with liver injury induced by Lieber-Decarli liquid diet and LPS.

[Preparation of Lieber-DeCarli liquid diet induced alcoholic hepatic injury model in rats].

OBJECTIVE: Duplicating the classical alcoholic hepatic injury model, to provide an ideal animal model for research on prevention and treatment of hepatic injury. METHODS: According to the prescription of Lieber-DeCarli, the same calorie fluid animal feed, which contained ethanol or non-ethanol, was prepared. Twenty-three rats were divided into normal control group (n=5), control liquid diet group (n=9), ethanol liquid diet group (n=9). Rats in the normal control group were fed normal diet, and rats in the control liquid diet group and ethanol liquid diet group were fed the corresponding diet for eight weeks. The pathologic changes of hepatic tissue were observed. The activities of the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the liver tissue gamma-glutamyltransferase (gamma-GT), the content of triglyceride (TG), and the lipid peroxidation by-products were assayed. RESULTS: Compared to the normal control and the control liquid diet groups, the activities of ALT, AST, and gamma-GT, and the lipid peroxidation by-products increased significantly in the ethanol liquid diet group. The pathological changes of cellular swelling and fatty degeneration in the ethanol liquid diet group were severe. CONCLUSION: Alcoholic hepatic injury model can be successfully duplicated by Lieber-DeCarli prescription.

[Relationship between alcoholic liver injury and endotoxin leakage from gut and intervention effect of jianpi liqi huoxue decoction].

OBJECTIVE: To study the effects and mechanisms of Jianpi Liqi Huoxue Decoction (JLHD) in anti-alcoholic liver injury (ALI) through the pathological relation of ALI with changes of intestinal permeability and endotoxin leakage. METHODS: The liver injury model induced by Lieber-DeCarli alcoholic forage was established. Altogether 42 male SD rats were randomly divided into 4 groups, the normal group (n=6), the control group fed with non-alcohol diet (n=12), the model group fed with alcoholic diet (n=12) and the treated group fed with alcoholic diet and treated with JLHD (n=12). The medicine or distilled water was administered by gavage from the 3rd week to the end of the 6th week. Then after fasting for 5 h all the rats except those in the normal group were given lipopolysaccharide (LPS) 10 mg/kg by gavage, and the blood plasma from portal vein, serum from inferior cava vein as well as tissues of liver and intestine were prepared for detection of plasma LPS level in the portal vein to observe the change of intestinal permeability through LPS content in portal vein blood plasma, the pathological and ultrastructural changes of the small intestine by HE staining, the pathological change of liver and triglyceride (TG) content and gamma glutamyl transpeptidase (GGT) activity in liver, the changes of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity, and plasma tumor necrosis factor-alpha (TNF-alpha) level. RESULTS: In rats after modeling, there were obvious fatty degeneration, significant increase of hepatic TG content and GGT activity, serum ALT and AST activity, as well as plasma TNF-alpha level, with high plasma LPS level indicating increased intestinal permeability, and seriously injured mucosa microvilla of small intestine. However, all the above abnormal changes were milder in the treated group than those in the model group. Meanwhile, the TNF-alpha content, endotoxin level and ALT activity were found to be positively correlated. CONCLUSION: JLHD could alleviate liver injury through inhibiting the alcohol induced increased intestinal permeability and lessening endotoxin leakage.

Intervention effects of Jianpi Liqi Huoxue Decoction on lipid peroxidative liver injury induced by alcohol.

OBJECTIVE: To study the intervention effects of Jianpi Liqi Huoxue Decoction ( JLHD) on lipid peroxidative liver injury induced by alcohol. METHODS: The rat alcoholic model of liver disease (ALD) induced by Lieber-DeCarli liquid diet was established. Thirty-two male SD rats were randomly divided into 4 groups: the normal group (n =5), the control group (n =9), the model group (n =9) and the JLHD group (n =9). From the 4th week after modeling, the rats were given JLHD or distilled water by gastrogavage respectively, and the samples of blood and liver tissues were taken out from the rats for determination by the end of the 8th week. The hepatic pathological changes were observed with HE staining; the liver injury related indices, including activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum, Y-glutamyl transpeptidase (Y-GT) activity and triglyceride (TG) content in liver tissues, as well as the lipid peroxidation related indices, including malonaldehyde (MDA) content and nitric oxide synthase (NOS) activity in liver tissue, serum Fe2+ level, and the anti-peroxidation capacity related indices, including superoxide dismutase (SOD) activity, glutathion (GSH) content and reactive oxygen species (anti-ROS) activity in liver tissues were determined. RESULTS: (1) There were obvious figures of fatty degeneration and inflammatory infiltration in liver tissues of the model group. As compared with the control group, in the model group, the activity of ALT and AST, and Fe2+ content in serum, Y-GT and NOS activity, TG and MDA content in liver tissues were significantly higher (P<0. 01), while the activity of SOD, GSH and anti-ROS in liver tissues were significantly lower (P<0.01). (2) The fatty degeneration and inflammatory infiltration of liver tissues in the JLHD group were significantly lessen as compared with those in the model group; and the abnormalities of all the indexes revealed in the model rats were restored to certain extent in the JLHD group, and especially significant were the levels of ALT activity, MDA content and Fe2+ , which were nearly normal. CONCLUSION: JLHD has significant effects against alcoholic liver injury, the acting mechanism of which is likely to be related with its anti-lipid peroxidative effect.

[Clinical investigation on characteristics of traditional Chinese medical syndrome of hepatocirrhosis].

OBJECTIVE: To explore the characteristics of traditional Chinese medical syndrome (TCM syndrome) of hepatocirrhosis. METHODS: Clinical information from the four diagnosis methods of traditional Chinese medicine (TCM) and related laboratorial indexes were systematically collected from 223 hepatocirrhosis cases, and the multi-statistical methods including systematic cluster analysis, principal component analysis, stepwise discrimination and variance analysis were made with the software SAS 6.11. RESULTS: Multi-analysis showed that there were 3 categories of syndrome characteristics. Type 1 (134 cases): damp heat, blood stasis, deficiency of liver and spleen Qi; Type 2 (62 cases): deficiency of both Qi and Yin with severe deficiency of Qi, heat with severe dampness, blood stasis; Type 3 (27 cases): deficiency of both Qi and Yin with severe deficiency of Yin, stasis and heat or dampness. Analysis of the changes of the related laboratorial indexes among the three types of syndrome showed that Type 1 mainly manifested asthenia syndrome with sthenia syndrome, and its indexes of AST, ALT, GGT levels were markedly higher than those of Type 2 and Type 3, both of which mainly showed sthenia syndrome with asthenia syndrome, and that Type 3 was in active inflammation, deficiency of both Qi and Yin (deficiency of Yin > deficiency of Qi), and its FN, Alb, FV, FVII, PLT, PCT levels were obviously reduced. CONCLUSION: The multi-statistical methods can reveal the characteristics and regularity of TCM syndrome of hepatocirrhosis, and the 3 categories of syndrome characteristics basically conform to clinical manifestations. The result of TCM syndrome distribution and laboratorial indexes infer that damp heat is the pathological basis of hepatocirrhosis, and the degree of liver function disorder and liver damage may be the pathological basis of deficiency of Yin of both liver and kidney.