BACKGROUND RAS , BRAF , and mismatch repair (MMR)/microsatellite instability (MSI) are crucial biomarkers recommended by clinical practice guidelines for colorectal cancer (CRC). However, their characteristics and influencing factors in Chinese patients have not been thoroughly described. AIM To analyze the clinicopathological features of KRAS , NRAS , BRAF , and PIK3CA mutations and the DNA MMR status in CRC. METHODS We enrolled 2271 Chinese CRC patients at the China-Japan Friendship Hospital. MMR proteins were tested using immunohistochemical analysis, and the KRAS/NRAS/BRAF/PIK3CA mutations were determined using quantitative polymerase chain reaction. Microsatellite status was determined using an MSI detection kit. Statistical analyses were conducted using SPSS software and logistic regression. RESULTS The KRAS , NRAS , BRAF , and PIK3CA mutations were detected in 44.6%, 3.4%, 3.7%, and 3.9% of CRC patients, respectively. KRAS mutations were more likely to occur in patients with moderate-to-high differentiation. BRAF mutations were more likely to occur in patients with right-sided CRC, poorly differentiated, or no perineural invasion. Deficient MMR (dMMR) was detected in 7.9% of all patients and 16.8% of those with mucinous adenocarcinomas. KRAS , NRAS , BRAF , and PIK3CA mutations were detected in 29.6%, 1.1%, 8.1%, and 22.3% of patients with dMMR, respectively. The dMMR was more likely to occur in patients with a family history of CRC, aged < 50 years, right-sided CRC, poorly differentiated histology, no perineural invasion, and with carcinoma in situ , stage I, or stage II tumors. CONCLUSION This study analyzed the molecular profiles of KRAS , NRAS , BRAF , PIK3CA , and MMR/MSI in CRC, identifying key influencing factors, with implications for clinical management of CRC.

Background: Osteosarcoma cells are prone to metastasis, and the mechanism of N6-methyladenosine (m6A) methylation modification in this process is still unclear. Methylation modification of m6A plays an important role in the development of osteosarcoma, which is mainly due to abnormal expression of enzymes related to methylation modification of m6A, which in turn leads to changes in the methylation level of downstream target genes messenger RNA (mRNA) leading to tumor development. Methods: We analyzed the expression levels of m6A methylation modification-related enzyme genes in GSE12865 whole-genome sequencing data. And we used shRNA (short hairpin RNA) lentiviral interference to interfere with METTL3 (Methyltransferase 3) expression in osteosarcoma cells. We studied the cytological function of METTL3 by Cell Counting Kit-8 (CCK8), flow cytometry, migration and other experiments, and the molecular mechanism of METTL3 by RIP (RNA binding protein immunoprecipitation), Western blot and other experiments. Results: We found that METTL3 is abnormally highly expressed in osteosarcoma and interferes with METTL3 expression in osteosarcoma cells to inhibit metastasis, proliferation, and apoptosis of osteosarcoma cells. We subsequently found that METTL3 binds to the mRNA of CBX4 (chromobox homolog 4), a very important regulatory protein in osteosarcoma metastasis, and METTL3 regulates the mRNA and protein expression of CBX4. Further studies revealed that METTL3 inhibited metastasis of osteosarcoma cells by regulating CBX4. METTL3 has been found to be involved in osteosarcoma cells metastasis by CBX4 affecting the protein expression of matrix metalloproteinase 2 (MMP2), MMP9, E-Cadherin and N-Cadherin associated with osteosarcoma cells metastasis. Conclusions: These results suggest that the combined action of METTL3 and CBX4 plays an important role in the regulation of metastasis of osteosarcoma, and therefore, the METTL3-CBX4 axis pathway may be a new potential therapeutic target for osteosarcoma.

Alpinia zerumbet is a food flavor additive and a traditional medicine herb around the world. Several studies have reported that A. zerumbet has excellent effects on a variety of cardiovascular diseases, but its potential hypertensive applications, and pharmacokinetic features of main active substances have not been fully investigated. The mechanism of anti-hypertension with ethyl acetate extracts of A. zerumbet fruits (AZEAE) was evaluated by L-NNA-induced hypertensive rats and L-NAME-injured human umbilical vein endothelial cells (HUVECs). Blood pressure, echocardiographic cardiac index and H&E staining were used to preliminary evaluate the antihypertensive effect of AZEAE, the levels of TNF-α, IL-6, and IL-1β were evaluated by ELISA, and the proteins expression of IL-1β, IL-18, AGTR1, VCAM, iNOS, EDN1 and eNOS were also evaluated. In addition, isolation, identification, and activity screening of bioactive compounds were carried ou. Next, pharmacokinetics and tissues distribution of dihydro-5,6-dehydrokavain (DDK) in vivo were measured, and preliminary absorption mechanism was conducted with Caco-2 cell monolayers. AZEAE remarkably enhanced the state of hypertensive rats. Twelve compounds were isolated and identified, and five compounds were isolated from this plant for the first time. The isolated compounds also exhibited good resistance against injury of HUVECs. Moreover, pharmacokinetics and Caco-2 cell monolayers demonstrated AZEAE had better absorption capacity than DDK, and DDK exhibited differences in tissues distribution and gender difference. This study was the first to assess the potential hypertensive applications of A. zerumbet in vivo and vitro, and the first direct and concise study of the in vivo behavior of DDK and AZEAE.

Abstract Colitis‐associated bowel cancer (CAC) is one of the most common malignancies associated with inflammation. The aim of this study was to observe a new herbal formula “Xiaotan Sanjie Fang” (XTSJF) derived from the addition and subtraction theory of traditional medicine as an alternative to CAC treatment by “Daotan Decoction” and “Xiaojianzhong Decoction”, which are famous traditional Chinese medicine prescriptions for the treatment of inflammatory diseases of the digestive tract. We constructed a DMH/DSS inflammation‐associated colorectal cancer rat model and treated CAC rats with sulfasalazine and different doses of XTSJF. The results showed that the body weight of rats treated with different doses of XTSJF increased, which was still lower than that of normal rats; AFC decreased significantly compared with the model group and the positive control group, and the final dose was superior to the low dose; histological observation revealed that it could maintain the normal structure of colon tissue, while it could inhibit the secretion of VEGF, COX2, and AQP1 and the expression of pro‐inflammatory cytokines IL‐6, IL‐1β, and TNF‐α, promote the expression of caspase‐3 and BAX and inhibit the expression of Bcl‐2. Taken together, these data suggest that XTSJF can inhibit COX‐2/VEGF expression to prevent the development of inflammation‐associated colorectal cancer.

6054 Background: Medullary thyroid carcinoma (MTC) is a rare malignancy, and its molecular pathogenesis is far from being understood. Therefore, a relatively comprehensive and accurate genomic profiling is needed for the future molecular diagnosis, treatment and early prevention of MTC patients. Methods: In this study, we investigated both the somatic and germline mutational spectrum of MTC, whole-exome sequencing (WES) was performed on tumor samples and matched noncancerous tissues from 30 MTC patients. Genetic alterations were defined and analyzed using MutSigCV and novel germline mutations were identified using MutationTaster and cross-referenced in PubMed. Results: In somatic mutational spectrum we found the top three significantly mutated genes (SMGs) in our MTC samples were RET, FAM186A and PRG4 genes (33%, 33% and 27%, respectively). For the germline mutations, FAT4 was detected as the most common mutated genes, following by RET and FAT1. Besides, we identified 30 novel germline mutations such as IGF1R, PDK1, NOTCH1, RPTOR, MPL, SETD2 and ARID2. Those mutated genes have been previously associated with neurofibromatosis, Lynch syndrome and other diseases respectively and now predicted potential functional pathogenicity in the patients with MTC. Conclusions: The study elucidated a relatively more comprehensive genomic landscape of MTC. In addition to the RET gene, which has been studied extensively, other SMGs may also be of interest including novel germline mutations. These findings may indicate the potential basis of molecular diagnosis, early prevention and targeted therapeutic options for patients with MTC in the future.

Background: Cancer-associated fibroblasts (CAFs) play an important role in the tumorigenesis, immunosuppression and metastasis of colorectal cancer (CRC), and can predict poor prognosis in patients with CRC. The present study aimed to construct a CAFs-related prognostic signature for CRC. Methods: The clinical information and corresponding RNA data of CRC patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The Estimation of STromal and Immune cells in MAlignant Tumor tissues (ESTIMATES) and xCell methods were applied to evaluate the tumor microenvironment infiltration from bulk gene expression data. Weighted gene co-expression network analysis (WGCNA) was used to construct co-expression modules. The key module was identified by calculating the module-trait correlations. The univariate Cox regression and least absolute shrinkage operator (LASSO) analyses were combined to develop a CAFs-related signature for the prognostic model. Moreover, pRRophetic and Tumor Immune Dysfunction and Exclusion (TIDE) algorithms were utilized to predict chemosensitivity and immunotherapy response. Human Protein Atlas (HPA) databases were employed to evaluate the protein expressions. Results: ESTIMATES and xCell analysis showed that high CAFs infiltration was associated with adverse prognoses. A twenty-gene CAFs-related prognostic signature (CAFPS) was established in the training cohort. Kaplan-Meier survival analyses reveled that CRC patients with higher CAFs risk scores were associated with poor prognosis in each cohort. Univariate and multivariate Cox regression analyses verified that CAFPS was as an independent prognostic factor in predicting overall survival, and a nomogram was built for clinical utility in predicting CRC prognosis. Patients with higher CAFs risk scores tended to not respond to immunotherapy, but were more sensitive to five conventional chemotherapeutic drugs. Conclusion: In summary, the CAFPS could serve as a robust prognostic indicator in CRC patients, which might help to optimize risk stratification and provide a new insight into individual treatments for CRC.

Blackberry is widely used in diets for its rich biological phytochemicals and health benefits. However, the relationship between the effect of blackberry extract (BBE) on ameliorating alcoholic liver disease (ALD) and the PXR-Cytochrome P450s axis in vivo and in vitro is unknown. In this study, 50% and 30% ethanol by gavage were used to establish acute and subacute ALD. Male mice were intragastrically administered BBE with 25, 50, and 100 mg/kg BW in the treatment groups. In the experiment, samples were collected, and related indices and histopathological observation were measured. In addition, the potential mechanism was predicted by network and docking studies, which were verified by qRT-PCR analysis, the detection of apoptosis, the measurement of mitochondrial membrane potential, the detection of ROS levels, and Western blotting in liver tissues and HepG2 cells. The acute and subacute ALD experiments indicated BBE ameliorated liver indices, AST, ALT, SOD, and MDA in serum, and the histopathology changed, as observed via H&E, Sirius red, and oil red O staining. The potential mechanism was predicted by network and docking studies, which were verified by experiments. Western blotting suggested BBE reduced the protein expression of NF-κB, TGF-β, IL-6, and α-SMA, and enhanced PXR and CAR in livers. In addition, qRT-PCR showed BBE significantly elevated the mRNA levels of PXR, CAR, CYP3A25, CYP3A11, and CYP2B10. In the experiment of the ethanol-induced apoptosis of HepG2 cells, BBE reduced the apoptosis of HepG2 cells by boosting mitochondrial membrane potential, reducing the apoptotic rate and ROS content, lessening the expression of Bax, and inducing the expression of PXR. For the first time, this study demonstrated BBE’s preventive effects on ALD, which are associated with the antioxidation and stimulation of the PXR-Cytochrome P450s axis. In addition, BBE is available as a nutritional agent.

Patients with advanced gastric cancer experience rapid disease progression with limited survival, high mortality, and a lack of surgical options. Thus, radiochemotherapy or a combination of chemotherapeutics with targeted therapy is the mainstay of treatment. In comparison to the treatment of other malignant tumors, in gastric cancer, the development of molecularly targeted drugs has been relatively slow. Currently, there are two major classes of molecularly targeted drug regimens that have achieved a certain efficacy in clinical practice: anti-vascular endothelial growth factor (anti-VEGF) therapy and anti-epidermal growth factor receptor (anti-EGFR) therapy. Trastuzumab has been approved as the standard of care for first-line treatment in advanced human epidermal growth factor receptor 2 (HER2)-positive gastric cancer. Ramucirumab in combination with paclitaxel is the recommended regimen for second-line treatment, and apatinib is recommended as third-line treatment. This review summarizes the current status of targeted therapies in the treatment of gastric cancer and gives a perspective on the future.

The purpose of this study is to explore the anti-colorectal cancer of Xiaotansanjiefang, a famous traditional Chinese medicine, and its potential anti-cancer mechanism. In this study, the HCT116 cell spheres were prepared as in vitro study model. We found the Xiaotansanjiefang medication was able to inhibit the proliferation of HCT116 cell spheres in a dose-dependent manner, especially in 3 and 6 mg/ml Xiaotansanjiefang medication treated groups. We also found the high concentration of Xiaotansanjiefang medication could suppress the migration and promote the apoptosis of HCT116 cell spheres. Moreover, we found the expression of Jagged 1, Notch 3, Snail, and Hes 1 were decreased in HCT116 cell spheres treated with Xiaotansanjiefang medication. Furthermore, the proliferation and apoptosis behaviors of HCT116 cell spheres treated with Xiaotansanjiefang medication were reversed with the addition of Jagged 1 Fc chimera protein. The expression of Jagged 1, Notch 3, Snail, and Hes 1 were also increased again in HCT116 cells treated with Xiaotansanjiefang medication plus with Jagged 1 Fc chimera protein. The presented study may provide a promising strategy to treat and prevent colorectal cancer.

Background and Objective Neurotoxicity is a common side effect of oxaliplatin; the effect of current drugs such as methylcobalamin and gabapentine is not obvious. Astragaloside IV (AS-IV) is an important active ingredient of Astragali Radix, which can protect the nervous system and inhibit tumor growth to a certain extent. However, whether AS-IV can reduce oxaliplatin neurotoxicity and its molecular mechanism remain unclear. Methods The network pharmacology method was used to determine the collective targets of AS-IV and oxaliplatin neurotoxicity. The model of neurotoxicity was established by intraperitoneal injection of oxaliplatin in rats. Bodyweight, mechanical withdrawal threshold (MWT), cold allodynia, and nerve conduction velocity (NCV) were examined, pathological changes were observed by hematoxylin-eosin staining, number of Nissl bodies were assessed by Nissl staining, the key collective targets were measured by spectrophotometry and immunohistochemistry. Results Through network pharmacological analysis, 25 collective targets of AS-IV and oxaliplatin neurotoxicity were identified, mainly related to inflammation and oxidative stress. AS-IV could increase body weight, elevate MWT, and reduce cold allodynia of model rats, it also raised NCV. Neuropathology was improved and the number of Nissl bodies was increased by AS-IV administration. It reduced TNF-α, IL-6, and IL-1β in the spinal cord of model rats to inhibit inflammation; it also decreased MDA, raised SOD, CAT, and GSH-Px in the spinal cord of model rats to block oxidative stress. Conclusion AS-IV improves oxaliplatin neurotoxicity by regulating neuroinflammation and oxidative stress; the results can provide a new perspective for the potential treatment strategy of oxaliplatin neurotoxicity.

BACKGROUND:Effective methods to deliver therapeutic genes to solid tumors and improve their bioavailability are the main challenges of current medical research on gene therapy. The development of efficient non-viral gene vector with tumor-targeting has very important application value in the field of cancer therapy. Proteolipid integrated with tumor-targeting potential of functional protein and excellent gene delivery performance has shown potential for targeted gene therapy.RESULTS:Herein, we prepared transferrin-modified liposomes (Tf-PL) for the targeted delivery of acetylcholinesterase (AChE) therapeutic gene to liver cancer. We found that the derived Tf-PL/AChE liposomes exhibited much higher transfection efficiency than the commercial product Lipo 2000 and shown premium targeting efficacy to liver cancer SMMC-7721 cells in vitro. In vivo, the Tf-PL/AChE could effectively target liver cancer, and significantly inhibit the growth of liver cancer xenografts grafted in nude mice by subcutaneous administration.CONCLUSIONS:This study proposed a transferrin-modified proteolipid-mediated gene delivery strategy for targeted liver cancer treatment, which has a promising potential for precise personalized cancer therapy.

Colorectal cancer (CRC) is one of the common malignant tumors, the incidence of which is on rise. LncHOTAIR, considered as an oncogene, contributed to the progression of a lot of cancers. However, the molecular mechanism and biological functions of the HOTAIR/miR-206/CCL2 axis have not been reported before. Here, our research aimed to explore HOTAIR/miR-206/CCL2 axis in CRC to demonstrate its role in predicting the poor prognosis of CRC. LncHOTAIR, miR-206 and CCL2 mRNA were detected in CRC tissues and cells by RT-PCR. The interactions among LncHOTAIR, miR-206 and CCL2 were explored by luciferase reporter assay, qRT-PCR, western blot and RNA interfere. Flow Cytometry Cell Analysis was performed to detect cell cycle and apoptosis as well as colony assay was prepared to test the cell proliferation. Immunohistochemical analysis was used to detect the CCL2 protein in CRC tissues. In our study, silence of LncHOTAIR by RNA interference could suppress the proliferation, migration and invasion of CRC cells. Mechanistically, LncHOTAIR downregulated miR-206 abundance which indicated that LncHOTAIR was considered as a competing endogenous RNA (ceRNA) by directly sponging miR-206 in CRC cells. In addition, further exploration suggested that miR-206 could inhibit the function of the downstream CCL2, the expression of which was repressed by LncHOTAIR/miR-206 signaling. Furthermore, we verified that the overexpression of CCL2 attenuated CRC cell proliferation, migration, invasion. Overall, this study firstly elucidated that LncHOTAIR played as oncogene in CRC via directly sponging miR-206 to activate the downstream CCL2, which would be considered as the novel therapeutic target in CRC.

Purpose The aim of this study was to develop an avidin-modified macromolecular lipid magnetic sphere and its application in differential diagnosis of liver disease and liver cancer. Materials and Methods Lectin-modified macromolecular lipid magnetic spheres were prepared by thin-film hydration method using lentil lectin derivatives (LCA-HQ) and cholesterol as raw materials. Alpha-fetoprotein variants (AFP-L3) in serum from healthy people, liver disease and liver cancer patients were isolated using the prepared lectin-modified macromolecular lipid magnetic spheres, and alpha-fetoprotein (AFP) and AFP-L3 were detected by fully automatic time-resolved fluorescence immunoassay. Results The lectin polymer lipid magnetic sphere prepared in this study was superparamagnetic and encapsulated by a lectin derivative. There was no significant difference in the recovery rate of AFP-L3 between avidin magnetic ball-automatic time-resolved fluorescence immunoassay and manual micro-affinity column method (p>0.05). We found that AFP-L3 can be used as a differential indicator between liver cancer and liver disease. The positive rate of AFP and AFP-L3 in liver cancer patients was higher than that in healthy people and liver disease patients (p<0.001). The AUC (95% CI) of AFP and AFP-L3 were 0.743 ± 0.031 and 0.850 ± 0.024, respectively. AFP-L3 AUC value is greater than AFP; therefore, AFP-L3 distinguishes liver cancer more accurately, and the difference is statistically different, p<0.05. Conclusion We proposed a novel method for integration of the lectin polymer lipid magnetic spheres and time-resolved fluorescence immunoassay that enables simple, accurate and rapid determination of AFP-L3 in clinical samples. To be noted, fully automatic time-resolved fluorescence immunoassay compared with the commonly used techniques in clinical practice, the measurement procedure is simple and is expected to be used for the detection and accurate diagnosis of liver cancer.

OBJECTIVE:To investigate the anti-gastric precancerous lesions effect and mechanism of Traditional Chinese Medicine Jinlongshe (JLS) granules in ethanol extractive of A. manshuriensis (EEA)-induced gastric precancerous lesions rats.METHODS:A rat model with the part typical proliferation of the gastric epithelium mucosa was established by EEA. These rats received different doses of JLS granules treatment for four weeks. Bodyweight, histological and ultrastructural changes of gastric precancerous lesions were evaluated. The expression of Apelin and CD34 mRNA and proteins of the gastric tissue were analyzed by quantitative Realtime PCR, western blot and immunohistochemical staining.RESULTS:We found that the treatment of JLS granules prevented the bodyweight loss and improved behavioral abnormalities of rats that received EEA. The histological and ultrastructural analysis also showed that JLS granules ameliorated EEA induced gastric precancerous lesions in a dose-dependent manner. The expression levels of two critical proteins involved in the angiogenesis of gastric carcinoma, Apelin, and CD34, were significantly reduced by the treatment of JLS granules.CONCLUSION:Our results indicated that JLS could inhibit the expression of the Apelin and CD34 genes in rat gastric mucosa, which reversed gastric precancerous lesions.

Oxaliplatin is a first-line clinical drug in cancer treatment and its side effects of peripheral neuropathic pain have also attracted much attention. Neuroinflammation induced by oxidative stress-mediated activation of nuclear factor-kappa B (NF-kappa B) plays an important role in the course. Current studies have shown that curcumin has various biological activities like antioxidant, anti-inflammatory, antitumor and so on, while few studies were conducted about its role in oxaliplatin-induced peripheral neuropathic pain. The aim of this study is to verify the mechanism of curcumin alleviating oxaliplatin-induced peripheral neuropathic pain. Intraperitoneal injection with oxaliplatin (4 mg/kg body weight) was given to the rats twice a week and last for four weeks to establish the model rats. Gavage administration of curcumin (12.5, 25, and 50 mg/kg body weight, respectively) was conducted for consecutive 28d to explore the effects and potential mechanism. Our results showed that curcumin administration could increase mechanical withdrawal threshold and decrease the paw-withdrawal times of cold allodynia significantly; meanwhile, motor nerve conduction velocity (MNCV) and sense nerve conduction velocity (SNCV) were both increased and the injured neurons of the spinal cord were repaired. In addition, curcumin administration increased superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and reduced malondialdehyde (MDA). Moreover, the curcumin operation inhibited the activated of NF-kappa B and level of inflammatory factors like tumor necrosis factor-a (TNF-alpha), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6). In conclusion, these findings suggested that curcumin could alleviate oxaliplatin-induced peripheral neuropathic pain; the mechanism might be inhibiting oxidative stress-mediated activation of NF-kappa B and mitigating neuroinflammation.

Objective This study was performed to assess the influence of obesity on colorectal cancer (CRC) and investigate the efficacy of Xiaotan Tongfu (XTTF) decoction to CRC treatment. Methods BALB/C mice were used to establish an obesity-associated CRC model by a high-fat diet and tumor implantation. The tumors were harvested from mice inoculated with CT26 cell suspension. Body weight, liver weight, hepatic metastasis, and histological changes were observed. Immunohistochemical analysis and real-time polymerase chain reaction were performed to measure the levels of insulin-like growth factor 1 (IGF-1), IGF-1 receptor (IGF-1R), and IGF binding protein 3 (IGFBP-3). Results Obesity influenced the secretion of IGFs and aggravated CRC, while XTTF decoction inhibited the process of hepatic metastasis in CRC by upregulating the secretion of IGF-1/IGF-1R and downregulating the secretion of IGFBP-3. Conclusions This study provides evidence that XTTF decoction can serve as a candidate curative treatment for CRC.

In recent years, Chinese medicine has played an important role in the prognosis of gastric cancer. Precancerous lesions of gastric carcinoma (PLGC) is a class of gastric cancer which is closely related to the gastric mucosal pathology changes in the role of carcinogenic incentives, and plays key role in the progression of normal gastric mucosal cells into gastric cancerous cells. In current experiment, we explore the relationship between Chinese traditional medicine (Xiao Tan He Wei Decoction) and gastric cancer in the PLGC rat animal models and epithelial-mesenchymal transitioned GES-1 cells which were induced useing 1- Methyl-3-nitro-1-nitrosoguanidine (MNNG). PLGC rat model showed significant deterioration in the gastric mucosa with terrible growth rate in body weight and more atypical hyperplasia in gastric mucosa. MC cells, MNNG induced GES-1 cells which epithelial- mesenchymal-transition (EMT)-related proteins have a great change compare with normal GES-1 cells. The cells had characteristics of malignant cells including proliferation, invasion and metastasis ability. Our research founds that Xiao Tan He Wei Decoction could inhibit cell proliferation and increased apoptosis by increase the level of pro-apoptotic proteins like Bax and caspase-3 and decreased the level of anti-apoptotic protein Bcl-2, block the cells in G0/G1 phase simultaneously. Furthermore, Xiao Tan He Wei Decoction could inhibit nuclear factor kappa-light-chain-enhancer (NF-kB) activity and inhibit its transfer from the cytoplasm to the nucleus. However, when we incubated with NF-κB activator PMA, the effect of Xiao Tan He Wei Decoction was reversed. These results suggested that Xiao Tan He Wei Decoction could be used as a method for the treatment of gastric precancerous lesions, and possibly provide a theoretical basis for the clinical treatment of gastric cancer and gastric precancerous lesions.

Colorectal cancer (CRC) is the most common cancer diagnosed worldwide, and the development of metastases is a major cause of mortality. Accumulating evidence suggests that microRNAs are important in carcinogenesis by affecting the expression of genes that regulate cancer progression. A number of studies have shown that miR-206 is frequently downregulated in many human malignancies, including CRC, and is associated with a more malignant phenotype. Previous studies involving HeLa and C2C12 cells have validated the inhibitory mechanism of miR-206 via NOTCH3 targeting. However, whether or not the interplay between miR-206 and NOTCH3 also occurs in CRC is unknown. Therefore, we investigated the tumor suppressive and metastatic effects of miR-206 and its target, NOTCH3, in CRC. Based on the inverse association between the expression of miR-206 and NOTCH3 in CRC tissues, miR-206 mimics were transiently transfected into the SW480 (and its metastatic strain) and SW620 colon cancer cell lines. Upregulation of miR-206 inhibited cancer cell prolife-ration and migration, blocked the cell cycle, and activated apoptosis. The tumor suppressive capacity of miR-206 had a similar effect on CRC cells, although with a different metastatic potential, and may be explained by direct NOTCH3 signaling inhibition and indirect cross-talk with other signaling pathways involving CDH2 and MMP-9. These results support miR-206 as a tumor suppressor in CRC and suggest a potential therapeutic target for clinical intervention.

Chylous ascites, which can lead to peritonitis, intestinal obstruction, metabolic disorder, and even death from pyemia, is a rare complication of abdominal surgery. Currently, first-line treatment involves conservative management, which includes oral diet and total parenteral nutrition (TPN). However, the efficacy of these treatments cannot be guaranteed. For example, single diet control can result in consecutive drainage for up to 1 month, and salvage surgery is required for some invalid cases. Here, we report 6 cases of chylous ascites after abdominal surgery. In addition to diet control, we delivered traditional Chinese herbal medicine (TCHM) twice daily orally. The drainage volume of the chylous fistula showed an obvious decrease 1 day after the TCHM administration and all 6 patients completely recovered within 4 to 8 days (median: 5.5 days). Although relevant data are limited, our cases would suggest that TCHM could play an important role in the management of chylous ascites. However, randomized controlled trials are still needed to confirm its efficacy in a larger population.

AIMTo determine the underlying mechanisms of action and influence of Xiaotan Sanjie (XTSJ) decoction on gastric cancer stem-like cells (GCSCs).METHODSThe gastric cancer cell line MKN-45 line was selected and sorted by FACS using the cancer stem cell marker CD44; the stemness of these cells was checked in our previous study. In an in vitro study, the expression of Notch-1, Hes1, Vascular endothelial growth factor (VEGF), and Ki-67 in both CD44-positive gastric cancer stem-like cells (GCSCs) and CD44-negative cells was measured by Western blot. The effect of XTSJ serum on cell viability and on the above markers was measured by MTT assay and Western blot, respectively. In an in vivo study, the ability to induce angiogenesis and maintenance of GCSCs in CD44-positive-MKN-45- and CD44-negative-engrafted mice were detected by immunohistochemical staining using markers for CD34 and CD44, respectively. The role of XTSJ decoction in regulating the expression of Notch-1, Hes1, VEGF and Ki-67 was measured by Western blot and real-time polymerase chain reaction.RESULTSCD44(+) GCSCs showed more cell proliferation and VEGF secretion than CD44-negative cells in vitro, which were accompanied by the high expression of Notch-1 and Hes1 and positively associated with tumor growth (GCSCs vs CD44-negative cells, 2.72 ± 0.25 vs 1.46 ± 0.16, P < 0.05) and microvessel density (MVD) (GCSCs vs CD44-negative cells, 8.15 ± 0.42 vs 3.83 ± 0.49, P < 0.001) in vivo. XTSJ decoction inhibited the viability of both cell types in a dose-dependent manner in vitro. Specifically, a significant difference in the medium- (82.87% ± 6.53%) and high-dose XTSJ groups (77.43% ± 7.34%) was detected at 24 h in the CD44(+) GCSCs group compared with the saline group (95.42% ± 5.76%) and the low-dose XTSJ group (90.74% ± 6.57%) (P < 0.05). However, the efficacy of XTSJ decoction was reduced in the CD44(-) groups; significant differences were only detected in the high-dose XTSJ group at 48 h (78.57% ± 6.94%) and 72 h (72.12% ± 7.68%) when compared with the other CD44- groups (P < 0.05). Notably, these differences were highly consistent with the Notch-1, Hes1, VEGF and Ki-67 expression in these cells. Similarly, in vivo, XTSJ decoction inhibited tumor growth in a dose-dependent manner. A significant difference was observed in the medium- (1.76 ± 0.15) and high-dose XTSJ (1.33 ± 0.081) groups compared with the GCSCs control group (2.72 ± 0.25) and the low-dose XTSJ group (2.51 ± 0.25) (P < 0.05). We also detected a remarkable decrease of MVD in the medium- (7.10 ± 0.60) and high-dose XTSJ (5.99 ± 0.47) groups compared with the GCSC control group (8.15 ± 0.42) and the low-dose XTSJ group (8.14 ± 0.46) (P < 0.05). Additionally, CD44 expression was decreased in these groups [medium- (4.43 ± 0.45) and high-dose XTSJ groups (3.56 ± 0.31) vs the GCSC control (5.96 ± 0.46) and low dose XTSJ groups (5.91 ± 0.38)] (P < 0.05). The significant differences in Notch-1, Hes1, VEGF and Ki-67 expression highly mirrored the results of XTSJ decoction in inhibiting tumor growth, MVD and CD44 expression.CONCLUSIONNotch-1 may play an important role in regulating the proliferation of GCSCs; XTSJ decoction could attenuate tumor angiogenesis, at least partially, by inhibiting Notch-1.