On the Security of a PUF-Based Authentication and Key Exchange Protocol for IoT Devices.

Recently, Roy et al. proposed a physically unclonable function (PUF)-based authentication and key exchange protocol for Internet of Things (IoT) devices. The PUF protocol is efficient, because it integrates both the Node-to-Node (N2N) authentication and the Node-to-Server (N2S) authentication into a standalone protocol. In this paper, we therefore examine the security of the PUF protocol under the assumption of an insider attack. Our cryptanalysis findings are the following. (1) A legitimate but malicious IoT node can monitor the secure communication among the server and any other IoT nodes in both N2N authentication and N2S authentication. (2) A legitimate but malicious IoT node is able to impersonate a target IoT node to cheat the server and any other IoT nodes in N2N authentication and the server in N2S authentication, respectively. (3) A legitimate but malicious IoT node can masquerade as the server to cheat any other target IoT nodes in both N2N authentication and N2S authentication. To the best of our knowledge, our work gives the first non-trivial concrete security analysis for the PUF protocol. In addition, we employ the automatic verification tool of security protocols, i.e., Scyther, to confirm the weaknesses found in the PUF protocol. We finally consider how to prevent weaknesses in the PUF protocol.

Research progress in targeted therapies for gastric cancer.

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.

On Secure Simple Pairing in Bluetooth Standard v5.0-Part I: Authenticated Link Key Security and Its Home Automation and Entertainment Applications.

Bluetooth is an important technical standard for short-range and low-power wireless communication. The home automation and entertainment (HAE) systems often make use of Bluetooth technology to link different Bluetooth devices and form Bluetooth networks. The security concerns of the HAE systems are raised due to massive deployment of the Bluetooth devices. The Bluetooth standard mainly depends on the secure simple pairing (SSP) solution to protect the Bluetooth devices. Hence, we investigate the SSP solution according to the Bluetooth standard v5.0. The contributions are threefold. (1) A formal security model is proposed to evaluate SSP's association models and authenticated link key. (2) We formally analyze two SSP protocols and present the security requirements for basic cryptographic modules in these SSP protocols. (3) We discuss the typical SSP applications in the HAE systems. Our results are useful to not only evaluating and designing the SSP protocols but also enhancing the security of the HAE systems in which the Bluetooth access is available.

On Secure Simple Pairing in Bluetooth Standard v5.0-Part II: Privacy Analysis and Enhancement for Low Energy.

Bluetooth low energy devices are very popular in wireless personal area networks. According to the Bluetooth standard specifications, the low energy secure simple pairing (LESSP) protocol is the process by which the pairing devices negotiate the authenticated secret key. To violate the user privacy, the adversary can perhaps link the runs of the LESSP protocol to the targeted device, which usually relates to the specially appointed user. Hence, we investigate deep into the privacy of the LESSP protocol. Our main contributions are threefold: (1) We demonstrate that the LESSP protocol suffers from privacy vulnerability. That is, an adversary without any secret key is able to identify the targeted device by the LESSP protocol. (2) An improvement is therefore proposed to repair the privacy vulnerability in the LESSP protocol. (3) We develop a formal privacy model to evaluate the privacy vulnerabilities in the LESSP protocol and its improved versions. We further prove that our improvement on the LESSP protocol is private under the privacy model. In addition, the performance evaluation shows that our improvement is as efficient as the LESSP protocol. Our research results are beneficial to the privacy enhancement of Bluetooth systems in wireless personal area networks.

[Inhibitory effect of Xiaotan Sanjie Recipe on the microsatellite instability of orthotopic transplantation tumor in MKN-45 human gastric cancer nude mice].

OBJECTIVE: To study the inhibitory effect of Xiaotan Sanjie Recipe (XSR) on the microsatellite instability of orthotopic transplantation tumor in MKN-45 human gastric cancer nude mice. METHODS: The 3rd passage subcutaneous transplantation tumor was taken as the origin of the model by using MKN-45 human gastric cancer cell lines. MKN-45 human gastric cancer nude mouse model was established using OB glue adhesive method. Then 30 nude mice were divided into the model group, the XSR group, and the chemotherapy group. Mice in the XSR group were intragastrically given XSR at the daily dose of 0.4 mL. Mice in the chemotherapy group were intragastrically given Fluorouracil at the daily dose of 0.4 mL. No intervention was given to mice in the model group. After 6 weeks of medication, the tumor weight was measured, and the tumor inhibition rate calculated. The size, the peak height, and the peak area of 5 microsatellite instability sites were detected. RESULTS: The tumor inhibition rate was 40. 84% in the XSR group. The tumor weight was significantly lower in the XSR group than in the model group (P < 0.01), showing no statistical difference when compared with the chemotherapy group (P >0.05). The incidence of high microsatellite instability (MSI-H) in the model group was 70%, and the incidence of low microsatellite instability (MSI-L) was 30%. Microsatellite stable site tended be stable after 6 weeks of XSR treatment. CONCLUSION: XSR showed inhibition on microsatellite instable orthotopic transplantation tumor in MKN-45 human gastric cancer nude mice.

Xiaotan Sanjie decoction normalizes tumor permissive microenvironment in gastric cancer (Review).

Gastric cancer (GC) develops in a complex tissue environment, the tumor microenvironment (TME), which it relies on for persistent proliferation, migration, invasion and metastasis. Non­malignant stromal cell types within the TME are regarded as a clinical meaningful target with the lower risk of resistance and tumor relapse. Studies have revealed that the Xiaotan Sanjie decoction, which is formulated on the basis of the theory of phlegm syndrome, a Traditional Chinese Medicine concept, modulates released factors such as transforming growth factor­ß from tumor cells, immune cells, cancer­associated fibroblasts, extracellular matrix, as well as vascular endothelial growth factor involved in the process of angiogenesis within the TME. Clinical studies have also shown that the Xiaotan Sanjie decoction is associated with favorable survival and quality of life. The present review aimed to interpret the hypothesis that Xiaotan Sanjie decoction has the ability to normalize the GC tumor cells by influencing functions of stromal cells within the TME. The possible association between phlegm syndrome and the TME in GC was discussed in the present review. Overall, Xiaotan Sanjie decoction may be suitable to be added to tumor cell­directed agents or emerging immunotherapies becoming a desirable modality in the management of GC and acquire improved outcomes for patients with GC.

A chinese herbal formula to improve general psychological status in posttraumatic stress disorder: a randomized placebo-controlled trial on sichuan earthquake survivors.

Introduction. Posttraumatic stress disorder (PTSD) is accompanied by poor general psychological status (GPS). In the present study, we investigated the effects of a Chinese herbal formula on GPS in earthquake survivors with PTSD. Methods. A randomized, double-blind, placebo-controlled trial compared a Chinese herbal formula, Xiao-Tan-Jie-Yu-Fang (XTJYF), to placebo in 2008 Sichuan earthquake survivors with PTSD. Patients were randomized into XTJYF (n = 123) and placebo (n = 122) groups. Baseline-to-end-point score changes in the three global indices of the Symptom Checklist-90-Revised (SCL-90-R) and rates of response in the SCL global severity index (GSI) were the primary endpoints. A subanalysis of the nine SCL factors and the sleep quality score were secondary endpoints. Results and Discussion. Compared to placebo, the XTJYF group was significantly improved in all three SCL global indices (P = 0.001~0.028). More patients in the XTJYF group reported "much improved" than the placebo group (P = 0.001). The XTJYF group performed significantly better than control in five out of nine SCL factors (somatization, obsessive-compulsive behavior, depression, anxiety, and hostility (P = 0.001~0.036)), and in sleep quality score (P < 0.001). XTJYF produced no serious adverse events. These findings suggest that XTJYF may be an effective and safe treatment option for improving GPS in patients with PTSD.

Ziyin Huatan Recipe, a Chinese herbal compound, inhibits migration and invasion of gastric cancer by upregulating RUNX3 expression.

OBJECTIVES: Ziyin Huatan Recipe (ZYHT), a traditional Chinese medicine comprised of Lilii Bulbus, Pinelliae Rhizoma, and Hedyotis Diffusa, has shown promise in treating gastric cancer (GC). However, its potential mechanism has not yet been clearly addressed. This study aimed to predict targets and molecular mechanisms of ZYHT in treating GC by network pharmacology analysis and to explore the role of ZYHT in GC both in vitro and in vivo. METHODS: Targets and molecular mechanisms of ZYHT were predicted via network pharmacology analysis. The effects of ZYHT on the expression of metastasis-associated targets were further validated by Western blot and quantitative real-time polymerase chain reaction. To explore the specific molecular mechanisms of the effects of ZYHT on migration and invasion, the runt-related transcription factor 3 (RUNX3) gene was knocked out by clustered regularly interspaced short palindromic repeats/Cas9, and lentiviral vectors were transfected into SGC-7901 cells. Then lung metastasis model of GC in nude mice was established to explore the anti-metastasis effect of ZYHT. Western blot and immunohistochemistry were used to explore the impact of ZYHT on the expression of metastasis-related proteins with or without RUNX3 gene. RESULTS: The network pharmacology analysis showed that ZYHT might inhibit focal adhesion, migration, invasion and metastasis of GC. ZYHT inhibited the proliferation, migration and invasion of GC cells in vitro via regulating the expression of metastasis-associated targets. Knocking out RUNX3 almost completely reversed the cell phenotypes (migration and invasion) and protein expression levels elicited by ZYHT. In vivo studies showed that ZYHT inhibited the metastasis of GC cells to the lung and prolonged the survival time of the nude mice. Knocking out RUNX3 partly reversed the metastasis of GC cells to the lung and the protein expression levels elicited by ZYHT. CONCLUSION: ZYHT can effectively inhibit the invasion and migration of GC in vitro and in vivo, and its molecular mechanism may relate to the upregulation of RUNX3 expression.

Syndrome characteristics of traditional Chinese medicine: summary of a clinical survey in 767 patients with gastric cancer.

OBJECTIVE: The present study is a summary of syndrome types of gastric cancer in order of priority based on clinical practical situations, routine clinical syndrome differentiation and a large-sample clinical survey in 767 patients with gastric cancer. METHODS: Based on the six-type classification of gastric cancer in a previous study, a bedside syndrome differentiation diagnosis was made simultaneously by two attending doctors of traditional Chinese medicine (TCM to avoid possible diagnostic bias. A clinical differentiation survey form designed under the direction of epidemiologists was filled out by patients with gastric cancer in multiple centers, and the results were digitally valued and statistically analyzed. RESULTS: The symptoms and signs in each syndrome type of gastric cancer were ranked in order of priority as follows: distended pain, stringy pulse, eructation, mood-related pain, susceptibility to anger, acid regurgitation, hiccup, fullness sensation or distension after eating just a little, dizziness, thin pulse, abdominal enlargement, obstruction sensation after eating, moving pain, and uneven pulse in disharmony between liver and stomach; dark red tongue with little fur or a smooth surface, burning pain, rapid pulse, associated burning heat in anus, dry mouth, fissured tongue, thin pulse, tidal fever in the afternoon, nausea and vomiting, and night sweating in impairment of yin due to stomach heat; slender tongue fur, obstruction after eating, slow pulse, moderate pulse, rapid and irregular pulse, normal mood, abdominal pain, diarrhea, cold extremities, lower-extremity edema, cold intolerance, pale complexion, dizziness, emaciation, hiccup, silence, nausea, uneven pulse, acid regurgitation, fullness sensation or distension after eating just a little, vomiting, and constipation in deficiency-cold in spleen and stomach; uneven pulse, stabbing pain, tortuous sublingual vein, blue or purplish tongue, fixed pain, tarry stool or dark red stool, vomiting of dark red fluid, pale complexion, dry mouth without desire to drink, stringy pulse, white tongue fur, nausea, thin tongue fur, colic pain, hiccup, dizziness, acid regurgitation, bitter taste in mouth, slow pulse, rapid and irregular pulse, thin pulse, and pain relief by pressing in interior retention of toxin stagnation; slippery pulse, greasy and thick tongue fur, dry mouth without desire to drink, vomiting of bilious fluid, nausea, bitter taste in mouth, fullness sensation or distension after eating just a little, colic pain, and hiccup in stagnation of phlegm-dampness; abdominal pain relief by pressing, map-like tongue, thin pulse, weakness, yellowish complexion, dizziness, spontaneous sweating, fissured tongue, epigastric discomfort, night sweating, emaciation, cold intolerance, constipation, nausea, and dry tongue in deficiency of both qi and blood. CONCLUSION: The summarized syndrome types of gastric cancer from this study are consistent with the clinical situations and would prove to be more referential for TCM syndrome differentiation diagnosis and treatment of gastric cancer.

[Effects of Xiaotan Sanjie Decoction on expressions of interleukin-8 and its receptors in gastric tumor xenografts and gastric tissue adjacent to the tumor in mice].

OBJECTIVE: To explore the mechanisms of Xiaotan Sanjie Decoction (XTSJD), a compound traditional Chinese herbal medicine, in inhibiting the tumor growth and preventing recurrence by testing the protein expressions of interleukin-8 (IL-8) and its receptors chemokine receptor 1 (CXCR1) and chemokine receptor 2 (CXCR2) in gastric tumor xenografts and gastric tissue adjacent to the tumor in mice. METHODS: Fifty Kunming mice were randomly divided into normal group, normal saline (NS) group, Heat-clearing and Detoxicating Decoction (HCDD) group, tegafur (FT-207) group and XTSJD group. Except for mice in the normal group, S180 tumor block was transplanted into the gastric walls of the mice, and the mice were administered with corresponding medicine for 3 weeks. Weight of tumor xenografts was measured and tumor inhibition rate was calculated. IL-8 protein expression was tested by enzyme-linked immunosorbent assay. Expressions of CXCR1 and CXCR2 were tested by immunohistochemical method. RESULTS: The protein expressions of IL-8 and its receptors in tumor xenografts and gastric tissue adjacent to the tumor were markedly higher than those in the gastric tissue in normal mice (P<0.01); compared with HCDD and FT-207, XTSJD could significantly decrease the IL-8 protein expression in tumor xenografts and gastric tissue adjacent to the tumor (P<0.05); compared with FT-207, XTSJD could significantly decrease the CXCR1 protein expression in tumor xenografts (P<0.01), and XTSJD could also significantly decrease the CXCR1 protein expression in gastric tissue adjacent to the tumor as compared with HCDD and FT-207 (P<0.01); compared with HCDD and FT-207, XTSJD could significantly decrease the CXCR2 protein expression in tumor xenografts (P<0.01), and there was no significant difference among the three drug-treated groups in CXCR2 protein expression in gastric tissue adjacent to the tumor (P>0.05). CONCLUSION: XTSJD can decrease the protein expressions of IL-8 and its receptors in tumor xenografts and gastric tissue adjacent to the tumor. It may be one of the mechanisms of XTSJD in inhibiting the tumor growth and preventing recurrence.

[Effects of Xiaotan Sanjie Decoction-containing serum on proliferation and apoptosis of human gastric cancer cells MKN-45].

OBJECTIVE: To observe the effects of serum containing Xiaotan Sanjie Decoction, a compound traditional Chinese herbal medicine, on proliferation and apoptosis of human gastric cancer cell line MKN-45. METHODS: After coculturing MKN-45 cells with low-, medium- and high-dose Xiaotan Sanjie Decoction-containing serum, inverted microscope was utilized to observe morphological changes and counting chamber was used to count the MKN-45 cells; the proliferation of MKN-45 cells was determined by cell counting kit 8; Annexin V-fluorescein isothiocyanate/propidium iodide double label method was used to detect apoptosis rate of MKN-45 cells. RESULTS: Xiaotan Sanjie Decoction-containing serum significantly inhibited the proliferation of MKN-45 cells. The typical morphological changes of apoptotic MKN-45 cells were observed after treating with Xiaotan Sanjie Decoction-containing serum. The cell apoptosis was also observed by flow cytometry and the apoptosis rates of medium- and high-dose Xiaotan Sanjie Decoction-containing serum groups were higher than that of low-dose group. CONCLUSION: Xiaotan Sanjie Decoction-containing serum can inhibit the MKN-45 cell proliferation and induce cell apoptosis, which provides an experimental evidence for its treatment of human gastric cancer.

Xiaotan Jieyu Prescription Alleviates Breast Precancerous Lesions through PI3K/Akt Signaling Pathway.

METHODS: The successfully established breast precancerous lesion rat model and normal healthy rats were randomly assigned into the blank (BLA), model (MOD), XTJY-low (LD), XTJY-medium (MD), XTJY-high (HD), and tamoxifen (TAM) groups. Different concentrations of XTJY and saline were supplied by intragastric administration for 4 consecutive weeks to assess the protective effect of XTJY on the progress of the breast precancerous lesion in rats involving the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. RESULTS: In this study, it determined that 10 mg/each rat DMBA-combined estrogen and progesterone induction for 10 weeks was the optimal condition for the establishment of the breast precancerous lesion rat model. In vivo administration of XTJY or TAM was found to inhibit the development of the breast precancerous lesion, and the occurrence rate of breast invasive carcinomas was decreased by about 50%. Furthermore, XTJY or TAM markedly reduced protein expressions of PI3K and p-Akt and increased protein expressions of PTEN. CONCLUSION: These data indicated that XTJY can significantly alleviate the development of breast precancerous lesions by inhibiting the activation of the PI3K/Akt signaling pathway. XTJY may be a promising drug for the treatment of precancerous lesions in breast cancer.

OB glue paste technique for establishing nude mouse human gastric cancer orthotopic transplantation models.

AIM: To establish nude mouse human gastric cancer orthotopic transplantation models using OB glue paste technique. METHODS: Using OB glue paste technique, orthopic transplantation models were established by implanting SGC-7901 and MKN-45 human gastric cancer cell strains into the gastric wall of nude mice. Biological features, growth of the implanted tumors, the success rate of transplantation and the rate of auto-metastasis of the two models were observed. RESULTS: The success rates of orthotopic transplantation of the two models were 94.20% and 96%. The rates of hepatic metastasis, pulmonary metastasis, peritoneal metastasis, lymphocytic metastasis and splenic metastasis were 42.13% and 94.20%, 48.43% and 57.97%, 30.83% and 36.96%, 67.30% and 84.06%, and 59.75% and 10.53%, respectively. The occurrence of ascites was 47.80% and 36.96%. CONCLUSION: OB glue paste technique is easy to follow. The biological behaviors of the nude mouse human gastric cancer orthotopic transplantation models established with this technique are similar to the natural processes of growth and metastasis of human gastric cancer, and, therefore, can be used as an ideal model for experimental research of proliferative metastasis of tumors.

[Establishment of a fuzzy mathematical model for syndrome differentiation of gastric cancer].

OBJECTIVE: To probe into a method for establishing the fuzzy mathematical model for syndrome differentiation of gastric cancer. METHODS: According to the analysis of 769 cases of gastric cancer, the U-domain, syndrome type set V and the fuzzy relation of symptom and syndrome type were established. The fuzzy set of syndrome type was set up too. The fuzzy model for syndrome differentiation of gastric cancer was constructed by adopting close degree fuzzy set and the biggest attaching principle. RESULTS: The actual coincidence rate in incoordination between liver and stomach was 65.00%; in yin deficiency due to gastric heat was 72.22%; in deficiency-cold of spleen and stomach was 70.00%; in blood stasis accumulating with toxin was 57.14%; in phlegm accumulating with dampness was 53.33%; and in exhaustion of both qi and blood was 72.22%. The overall coincidence rate was 65.71%. CONCLUSION: The model offers a solution for objective research of syndrome differentiation, and has the clinical value.

Syndrome differentiation in traditional Chinese medicine and E-cadherin/ICAM-1 gene protein expression in gastric carcinoma.

AIM: To explore the syndrome differentiation in traditional Chinese medicine (TCM) and gene protein expression in gastric carcinoma. METHODS: Preoperative data of gastric cancer cases were collected from the General Surgery Department and classified according to the criteria for syndrome differentiation in TCM. E-cadherin (E-cad) and ICAM-1 gene protein expressions were detected in postoperative specimens from these cases by the immunohistochemical EnVision two-step method. RESULTS: The E-cad positive expression rate was 90% in 100 cases of gastric carcinoma. The difference in E-cad expression was significant between the different syndrome differentiation types in TCM (P < 0.01). Further group-group comparison showed that there was a significant difference in E-cad expression between the stagnation of phlegm-damp type and the deficiency in both qi and blood and the deficiency-cold of stomach and spleen types, where E-cad expression was high. There was no significant difference between the internal obstruction of stagnant toxin type and the in-coordination between liver and stomach type, where E-cad expression was relatively low. The ICAM-1 positive expression rate was 58%, and there was no statistically significant difference between the two groups (c2 = 8.999, P > 0.05). CONCLUSION: E-cad expression is relatively low in the internal obstruction of stagnant toxin type and the in-coordination between liver and stomach type, where tumor development and metastasis may be associated with low E-cad expression, or with low homogeneous adhesiveness between tumor cells.

Anticancer effects of traditional Chinese herbs with phlegm-eliminating properties - An overview.

ETHONOPHARMACOLOGICAL RELEVANCE: Cancer is considered to be the second leading cause of human death. It is unsatisfactory that in the past decades, the treatment for cancer has not progressed as fast as it was expected, as only 50% of newly diagnosed patients could be cured even today. The development of cancer is a multifactorial process, involving tumor cells themselves, the interactions between tumor cells and their microenvironments, as well as the interactions between tumor cells and the host's immunity. Focusing on any single goal may bring limited benefits. AIM AND METHODS OF THE STUDY: Phlegm-eliminating herbs, which can reduce phlegm and eliminate pathological metabolites, are commonly used to treat cancer in China. However, the underlying molecular targets and efficacy of herbal medicines in cancer treatment still remain unclear. In this study, we reviewed the potential anticancer mechanisms of some phlegm-eliminating herbs and their active ingredients from the articles through such scientific databases as MEDLINE, PubMed, and Google Scholar. RESULTS: We found that the anticancer mechanisms of phlegm-eliminating herbs and ingredients include inducing apoptosis, anti-proliferation, preventing tumor invasion and metastasis, and reducing resistance to chemotherapy. In addition, some phlegm-eliminating herbs and their ingredients have anti-inflammatory and anti-metabolic syndrome effects. CONCLUSIONS: We suggest that the phlegm-eliminating herbs and ingredients are potential candidates for anticancer treatment and cancer prevention by playing a comprehensive role.

Therapeutic effect of Jinlongshe Granule () on quality of life of stage IV gastric cancer patients using EORTC QLQ-C30: A double-blind placebo-controlled clinical trial.

OBJECTIVE: To evaluate the impact of Jinlongshe Granule (, JLSG) on quality of life (QOL) of stage IV gastric cancer patients. METHODS: This randomized, double-blind and placebo-controlled clinical trial included 50 patients with advanced gastric cancer. They were equally randomized into a JLSG group and a placebo group. Patients in both groups received routine Chinese herbal decoctions according to Chinese medicine (CM) treatment based on syndrome differentiation. Patients in JLSG group received additional JLSG, and those in the placebo group received an additional placebo. In the JLSG group, 19 patients who completed the study were used for analysis. In the placebo group, finally the data of 20 patients who completed the study were used for analysis. The treatment course was at least 3 months, and the follow-up duration was at least 6 months in 5 interviews. Repeated measurements of the subscale items and individual items in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire C30 (EORTC QLQ-C30) obtained at the 5 interviews were compared using different patient groups, changes over time and changes within one group over time independently to observe the tendency of changes in the scores. RESULTS: Using time as the variant, there was signifificant difference in 4 functional scales (physical, role, emotional and social, P<0.05), 3 symptom scales (fatigue, nausea and vomiting and pain,P<0.05) and a global health status/QOL scale (P<0.05) and 6 single symptoms dyspnoea (P>0.05), insomnia (P<0.05), appetite loss (P<0.05), constipation (P<0.05), diarrhea (P>0.05) and financial difficulties (P<0.05). There was also signifificant difference in these items between the two groups when the placebo group and group over time were used as variants (P<0.05 or P<0.01). CONCLUSION: Additional use of JLSG on the basis of routine CM treatment could improve the somatic function, role function, emotional function, social function, cognitive function and general QOL of patients with advanced gastric cancer, and relieve the symptoms of fatigue, nausea and vomiting, pain, loss of appetite and constipation.

Xiaotan Sanjie decoction attenuates tumor angiogenesis by manipulating Notch-1-regulated proliferation of gastric cancer stem-like cells.

AIM: To determine the underlying mechanisms of action and influence of Xiaotan Sanjie (XTSJ) decoction on gastric cancer stem-like cells (GCSCs). METHODS: The 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. RESULTS: CD44(+) 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. CONCLUSION: Notch-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.