Effects of Traditional Chinese Medicine on the survival of patients with stage I gastric cancer and high-risk factors: a real-world retrospective study.

OBJECTIVE: To investigate the benefits of Traditional Chinese Medicine (TCM) therapy for improving the survival of patients with stage I gastric cancer (GC) and high-risk factors in a real-world setting. METHODS: The clinical data of patients who were diagnosed with stage I GC from March 1, 2012 to October 31, 2020 were collected. Prognostic analysis was performed to explore the high-risk factors that affected the survival of the patients. A Cox multivariate regression model was used to compare the hazard ratios for the mortality risk of patients, especially those with high-risk factors. Kaplan-Meier survival curve and log-rank test were utilized to assess the survival time. RESULTS: Prognostic analysis demonstrated that female sex, tumor invasion into blood vessels, and Ib stage were independent risk factors. The 1-, 3-, and 5-year survival rates of the TCM group those of the non-TCM group were 100.0% 91.0%, 97.6% 64.5%, and 81.4% 55.5%, respectively. A significant difference in median overall survival (mOS) was found between the two groups (χ = 7.670, = 0.006). Subgroup analysis showed that the mOS of female patients and stage Ib patients in the TCM group were longer than those in the non-TCM group ( ≤ 0.001 and 0.001, respectively). CONCLUSIONS: TCM treatment can improve the survival of patients with stage I GC and high-risk factors.

A survey of chronic pain in China.

There is an extensive body of research about chronic pain and treatment in developed countries. In contrast there is a lack of research on this topic in developing countries including China. This study was aimed to estimate the prevalence of chronic pain in different regions of China. Data on pain and its treatment were collected from 9357 participants using questionnaires and telephone-based interviews, from 31 regions of China. Gathered data were then coded into electronic data acquisition system and descriptive and inferential statistical analysis was performed. Out of 9298 participants, the ratio of chronic pain was 31.54% with the proportion of male having chronic pain (33.86%) was higher than that of female (29.53%). The average age of participants with pain (45.02 ± 15.07 years) was higher than free-pain participants (36.19 ± 11.12 years). There were also significant differences between groups in occupation, education levels, and illness history. Proportion of patients with pain duration of 1 year was 12.104%, between 1 and 5 years was 60%, and over 10 years was 10.74%. There were 63.9% of patients with moderate pain and 36.1% with severe pain. About 43.042% of patients thought that pain resulted in sleep disorder, 38.99% thought that it causes anxiety, and about 33% thought depression and irritable bowel was the result of their pain. For the chronic pain, more than half of patients used naprapathy, cupping, and other physical therapies. Up to 2016, the ratio of pain incidence was over 30% in China. The location of pain was focused on back and upper limb. There has been a lack of proper treatment. Patients with pain had obvious economic burden, and their quality of life and psychology were significantly affected.

COE inhibits vasculogenic mimicry in hepatocellular carcinoma via suppressing Notch1 signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Vasculogenic mimicry (VM) has been suggested to be present in various malignant tumors and associated with tumor nutrition supply and metastasis, leading to poor prognosis of patients. Notch1 has been demonstrated to contribute to VM formation in hepathocellular carcinoma (HCC). Celastrus orbiculatus extract (COE), a mixture of 11 terpenoids isolated from the Chinese Herb Celastrus orbiculatus Vine, has been suggested to be effective in cancer treatment. AIM OF THE STUDY: In the current study, experiments were carried out to examine the effect of COE on VM formation and HCC tumor growth both in vitro and in vivo. MATERIALS AND METHODS: CCK-8 assay and Nikon live-work station were used to observe the viability of malignant cells treated with COE. Cell invasion was examined using Transwell. Matrigel was used to establish a 3-D culture condition for VM formation. Changes of mRNA and protein expression were examined by RT-PCR and Western Blot respectively. Tumor growth in vivo was monitored using in vivo fluorescence imaging device. PAS-CD34 dual staining and electron microscopy were used to observe VM formation. Immunohistochemical staining (IHC) was used to examine Notch1 and Hes1 expression in tumor tissues. RESULTS: Results showed that COE can inhibit HCC cells proliferation and invasion in a concentration-dependent manner. VM formation induced by TGF-ß1 was blocked by COE. In mouse xenograft model, COE inhibited tumor growth and VM formation. Both in vitro and in vivo studies showed that COE can downregulate expression of Notch1 and Hes1. CONCLUSION: The current results indicate that COE can inhibit VM formation and HCC tumor growth by downregulating Notch1 signaling. This study demonstrates that COE is superior to other anti-angiogenesis agents and can be considered as a promising candidate in HCC treatment.

Notch1 promotes vasculogenic mimicry in hepatocellular carcinoma by inducing EMT signaling.

Hypervascularity is one of the main characteristics of hepatocellular carcinoma (HCC). However, the mechanisms of angiogenesis in HCC remain controversial. In this study, we investigate the role of Notch1 in angiogenesis of HCC. We found that Notch1 expression was correlated with formation of vasculogenic mimicry (VM) and expression of biomarkers of epithelial-to-mesenchymal transition (EMT) in the tumor specimens. Two HCC cell lines, HepG2 and MHCC97-H, with low and high Notch1 expression, respectively, were used to study the mechanism of VM formation both in vitro and in vivo. It was found that MHCC97-H cells, but not HepG2 cells form VM when they grow on matrigel in vitro. HepG2 cells gained the power of forming VM when they were overexpressed with Notch1, while knockdown Notch1 expression in MHCC97-H cells led to the loss of VM forming ability of the cells. Similar results were found in in vivo study. High expression of Notch1 in HepG2 promoted xenograft growth in nude mice, with abundant VM formation in the tumor samples. Moreover, we observed Notch1 was associated with the EMT and malignant behavior of hepatocellular carcinoma by analyzing clinical specimens, models for in vitro and in vivo experiments. HepG2 presented EMT phenomenon when induced by TGF-ß1, accompanied by Notch1 activation while MHCC97-H with knockdown of Notch1 lost the responsiveness to TGF-ß1 induction. Our results suggest that Notch1 promotes HCC progression through activating EMT pathway and forming VM. Our results will guide targeting Notch1 in new drug development.

Vasculogenic mimicry in hepatocellular carcinoma contributes to portal vein invasion.

Portal vein invasion (PVI) is common in hepatocellular carcinoma (HCC) and largely contributes to tumor recurrence after radical tumor resection or liver transplantation. Vasculogenic mimicry (VM) was an independent vascular system lined with tumor cells and associated with poor prognosis of HCC. The present study was conducted to evaluate the relationship between VM and portal vein invasion. A total of 44 HCC cases receiving anatomic liver resection were included in the study and were divided into groups with and without PVI. The prevalence of VM in each group was examined by CD34-PAS dual staining. The regulatory molecules of VM formation such as Notch1, Vimentin and matrix metalloproteinases (MMPs) were investigated by immunohistochemical staining. Analysis was performed to explore the association of PVI, VM and the VM regulatory molecules. PVI was found in 40.91% (18/44) cases and VM was found in 38.64% (17/44) cases in total samples. The incidence of VM was 72.22% (13/18) in PVI group while it was 15.38% (4/26) in non-PVI group (P<0.001), VM formation was positively correlated with PVI (r=0.574, P<0.001). The VM forming regulatory molecules such as Notch1, Vimentin, MMP-2 and MMP-9 were found to be correlated with PVI in HCC patients. Taken together, our results suggested that VM formation, alone with its regulatory molecules, is the promoting factor of PVI in hepatocellular carcinoma.