Correlation of Neuroendocrine Differentiation with a Distinctively Suppressive Immune Microenvironment in Gastric Cancer.

INTRODUCTION: Neuroendocrine neoplasms (NENs) harbored significantly suppressive tumor immune microenvironments (TIMEs). However, the immunological effects of neuroendocrine differentiation (NED) on non-NENs, such as gastric cancer (GC), were unknown. METHODS: Between pure gastric cancer (PGC) and GC-NED, TIME features were scored based on expression data and validated on serial whole-tissue sections of surgical samples, with tertiary lymphoid structures (TLSs) and the extra-TLS zone evaluated independently using multi-marker immunohistochemical staining. Risk analyses of TIME features on tumor behaviors were performed in GC-NED. The universal immunological effects of NED were explored preliminarily in adenocarcinomas arising in other organs. RESULTS: Based on over 11,500 annotated TLSs and 2,700 extra-TLS zones, compared with PGC, GC-NED harbored a distinctively more suppressive TIME characterized by increased but immature TLSs, with higher naïve B-cell and follicular regulatory T-cell densities and downregulated TLS maturation-related cell ratios inside TLSs; increased naïve B-cell and regulatory T-cell densities; and a high proportion of exhausted T cells in the extra-TLS zone. The upregulated tumor PD-L1 expression and its close correlations with TLS formation and maturation were remarkable exclusively in GC-NED. TIME features, especially those regarding TLSs, were significantly correlated with tumor growth and invasion. The desynchrony between TLS formation and maturation and increased naïve or regulatory immune cell infiltration was observed in adenocarcinomas of the colorectum, pancreas, lung, and prostate. CONCLUSION: NED highlighted a distinct GC entity with more suppressive TIME features correlated with tumor behaviors, indicating a cohort that would benefit more from immunotherapies.

A rare gastric lesion: diminutive, well-differentiated, Grade 3, type 3 gastric neuroendocrine tumor with extremely high ki-67 index removed en bloc under endoscopy.

Grade 3, type 3 gastric neuroendocrine tumor (g-NET) shows specific features of clinical interest and the therapeutic management of the lesion is not yet completely standardized. We present the unusual case of a 34-year-old male patient with a diminutive (less than 0.5 cm), well-differentiated, G3, type 3g-NET with extremely high Ki-67 index (higher than 80%). The lesion was subsequently removed en bloc via endoscopic submucosal dissection. Regarding the proliferation rate, Ki-67 index values usually range from 21 to 50%, and less commonly above 55%, in G3 NET. To our knowledge, this lesion represents a small size with the highest Ki-67 index diagnosed with G3 g-NET. However, as g-NET might recur even after a long duration, we recommend a long-term follow-up, such as 10 years after complete resection in patients to evaluate the endoscopic resection approach.

Adverse effects of low serum lipoprotein cholesterol on the immune microenvironment in gastric cancer: a case‒control study.

BACKGROUND: Cholesterol is crucial for tumor immune microenvironment (TIME) remodeling. Serum lipoprotein cholesterol is closely associated with gastric cancer (GC) progression, but whether it affects TIME remodeling is unknown. METHODS: GC patients with differential serum high-density lipoprotein (HDL) or low-density lipoprotein (LDL) cholesterol levels were collected. After balancing the baseline, immunohistochemical staining was performed on serial whole-tissue sections to detect B-cell and T-cell subsets, macrophages, and PD-L1. Features of tertiary lymphoid structures (TLSs) and the extra-TLS zone, including TLS distribution and maturation, immune cell density, and PD-L1 expression, were measured by annotating TLSs or regions of interest (ROIs) in the extra-TLS zone. RESULTS: A total of 9,192 TLSs and over 300 ROIs from 61 patients were measured. Compared to HDL-normal patients, HDL-low patients had a decreased secondary-TLS fraction or density but an elevated NK-cell density in the extra-TLS zone. Compared to LDL-normal patients, LDL-low patients had a higher ratio of PD-1 + T follicular helper cells to CD20 + B cells in TLSs, a higher ratio of PD-1 + T cells to CD8 + T cells and increased PD-1 + T-cell density in the extra-TLS zone. Different correlations were found in groups with differential HDL or LDL levels. Cell dynamics in the immune response were weaker in patients with low lipoprotein cholesterol. TLS parameters reached their peak earlier than those of the extra-TLS zone along with tumor progression. CONCLUSION: Low serum lipoprotein cholesterol caused adverse effects on antitumor immunity in GC. Lipid management or immunometabolic drugs deserve more attention.

Long-term Effects of the COVID-19 Pandemic on Public Sentiments in Mainland China: Sentiment Analysis of Social Media Posts.

BACKGROUND: The COVID-19 outbreak has induced negative emotions among people. These emotions are expressed by the public on social media and are rapidly spread across the internet, which could cause high levels of panic among the public. Understanding the changes in public sentiment on social media during the pandemic can provide valuable information for developing appropriate policies to reduce the negative impact of the pandemic on the public. Previous studies have consistently shown that the COVID-19 outbreak has had a devastating negative impact on public sentiment. However, it remains unclear whether there has been a variation in the public sentiment during the recovery phase of the pandemic. OBJECTIVE: In this study, we aim to determine the impact of the COVID-19 pandemic in mainland China by continuously tracking public sentiment on social media throughout 2020. METHODS: We collected 64,723,242 posts from Sina Weibo, China's largest social media platform, and conducted a sentiment analysis based on natural language processing to analyze the emotions reflected in these posts. RESULTS: We found that the COVID-19 pandemic not only affected public sentiment on social media during the initial outbreak but also induced long-term negative effects even in the recovery period. These long-term negative effects were no longer correlated with the number of new confirmed COVID-19 cases both locally and nationwide during the recovery period, and they were not attributed to the postpandemic economic recession. CONCLUSIONS: The COVID-19 pandemic induced long-term negative effects on public sentiment in mainland China even as the country recovered from the pandemic. Our study findings remind public health and government administrators of the need to pay attention to public mental health even once the pandemic has concluded.

Economic Burden and Health Care Access for Patients With Inflammatory Bowel Diseases in China: Web-Based Survey Study.

BACKGROUND: The increasing incidence of inflammatory bowel disease (IBD) has imposed heavy financial burdens for Chinese patients; however, data about their financial status and access to health care are still lacking. This information is important for informing patients with IBD about disease treatment budgets and health care strategies. OBJECTIVE: The aim of this study was to evaluate the economic status and medical care access of patients with IBD through the China Crohn's & Colitis Foundation web-based platform in China. METHODS: Our study was performed in 14 IBD centers in mainland China between 2018 and 2019 through WeChat. Participants were asked to complete a 64-item web-based questionnaire. Data were collected by the Wenjuanxing survey program. We mainly focused on income and insurance status, medical costs, and access to health care providers. Respondents were stratified by income and the associations of income with medical costs and emergency visit times were analyzed. RESULTS: In this study, 3000 patients with IBD, that is, 1922 patients with Crohn disease, 973 patients with ulcerative colitis, and 105 patients with undetermined colitis were included. During the last 12 months, the mean (SD) direct and indirect costs for per patient with IBD were approximately US $11,668.68 ($7944.44) and US $74.90 ($253.60) in China. The average reimbursement ratios for most outpatient and inpatient costs were less than 50%. However, the income of 85.5% (2565/3000) of the patients was less than ¥10,000 (US $1445) per month. Approximately 96.5% (2894/3000) of the patients were covered by health insurance, but only 24.7% (741/3000) of the patients had private commercial insurance, which has higher imbursement ratios. Nearly 98.0% (2954/3000) of the patients worried about their financial situation. Thus, 79.7% (2392/3000) of the patients with IBD tried to save money for health care and even delayed their medical treatments. About half of the respondents (1282/3000, 42.7%) had no primary care provider, and 52.2% (1567/3000) of the patients had to visit the emergency room 1-4 times per year for the treatment of their IBD. Multivariate analysis revealed that lower income (P=.001) and higher transportation (P=.004) and accommodation costs (P=.001) were significantly associated with the increased number of emergency visits of the patients. CONCLUSIONS: Chinese patients with IBD have enormous financial burdens and difficulties in accessing health care, which have increased their financial anxiety and inevitably influenced their disease outcomes. Early purchase of private insurance, thereby increasing the reimbursement ratio for medical expenses, and developing the use of telemedicine would be effective strategies for saving on health care costs.

Role of Bile Acids in Dysbiosis and Treatment of Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a major health threat around the world and is characterized by dysbiosis. Primary bile acids are synthesized in the liver and converted into secondary bile acids by gut microbiota. Recent studies support the role of bile acids in modulating dysbiosis and NAFLD, while the mechanisms are not well elucidated. Dysbiosis may alter the size and the composition of the bile acid pool, resulting in reduced signaling of bile acid receptors such as farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5). These receptors are essential in lipid and glucose metabolism, and impaired bile acid signaling may cause NAFLD. Bile acids also reciprocally regulate the gut microbiota directly via antibacterial activity and indirectly via FXR. Therefore, bile acid signaling is closely linked to dysbiosis and NAFLD. During the past decade, stimulation of bile acid receptors with their agonists has been extensively explored for the treatment of NAFLD in both animal models and clinical trials. Early evidence has suggested the potential of bile acid receptor agonists in NAFLD management, but their long-term safety and effectiveness need further clarification.

[Advances in serum biomarkers for early diagnosis of gastric cancer].

Early diagnosis is the key to improve the prognosis of gastric cancer. How to screen out high-risk subjects of gastric cancer in population is a hot spot. Serum-based early detection of gastric cancer is suitable for high-risk population screening, which is more convenient and safer. This article reviews the diagnostic value of serum biomarkers for gastric cancer, including serum DNA methylation, various RNAs, pepsinogen, gastrin, osteopontin, MG7-Ag and CA724. Until now, there is still lack of ideal biomarkers for gastric cancer, and searching for specific RNAs may be promising for early diagnosis and screening of gastric cancer.

Cholesterol Enhances Colorectal Cancer Progression via ROS Elevation and MAPK Signaling Pathway Activation.

BACKGROUND/AIMS: Elevated serum cholesterol levels were linked to a higher risk of colorectal adenoma and colorectal cancer (CRC), while the effect of cholesterol on CRC metastasis has not been widely studied. METHODS: CRC patients were enrolled to evaluate the association between low-density lipoprotein cholesterol (LDL) and CRC metastases, and LDL receptor (LDLR) level of the CRC tissue was assessed by immunohistochemistry. The effects of LDL on cell proliferation, migration and stemness were assessed in CRC cells in vitro, and the effects of high fat diet (HFD) on tumor growth and intestinal tumorigenicity were investigated in vivo. ROS assays, gene expression array analysis and western blot were used to explore the mechanisms of LDL in CRC progression. RESULTS: The level of LDL was positively correlated with liver metastases, and a higher level of LDL receptor (LDLR) expression was associated with advanced N and M stages of CRC. In vitro, LDL promoted the migration and sphere formation of CRC cells and induced upregulated expression of "stemness" genes including Sox2, Oct4, Nanog and Bmi 1. High-fat diet (HFD) significantly enhanced tumor growth in vivo, and was associated with a shorter intestinal length in azoxymethane/dextran sodium sulfate (AOM/DSS)-treated mice. Furthermore, LDL significantly elevated reactive oxygen species (ROS) levels and Whole Human Genome Microarray found 87 differentially expressed genes between LDL-treated CRC cells and controls, which were largely clustered in the MAP kinase (MAPK) signaling pathway. CONCLUSIONS: LDL enhances intestinal inflammation and CRC progression via activation of ROS and signaling pathways including the MAPK pathway. Inflammation is strongly associated with cancer initiation, and the role of LDL in intestinal tumorigenicity should be further explored.

Differential responses from the left postcentral gyrus, right middle frontal gyrus, and precuneus to meal ingestion in patients with functional dyspepsia.

Background: Functional dyspepsia (FD) is most often a meal-induced syndrome. Studies using resting-state functional magnetic resonance imaging (rs-fMRI) reported abnormal connectivity in areas related to pain processing in FD. However, only a few studies have attempted to determine how meal ingestion affects the brain's working patterns. Through rs-fMRI, this study observed how meal ingestion affected brain regions related to visceral hypersensitivity and emotional response networks in FD patients. Methods: A total of 30 FD patients and 32 healthy controls (HC) were enrolled and underwent clinical investigations. Rs-fMRI was performed twice after a 4-h fast and 50 min after a meal. The mean functional connectivity strength (FCS) values were extracted from brain regions with significant differences to show the trend of changes related to meal ingestion after FCS analyses. Results: Depression, anxiety, sleep disturbances, and weight loss were more common in FD patients (P ≤ 0.001). Compared with HCs (corrected cluster P-value < 0.05), FD patients had significantly higher FCS in the right middle frontal gyrus before meals and higher meal-induced FCS in the left postcentral gyrus. HCs had greater meal-induced activation in the right precuneus and anterior cingulate cortex. FD patients had a decreasing trend in the right inferior frontal gyrus compared to the increasing trend in HCs. We only found anxiety to be negatively correlated with FCS in the right inferior frontal gyrus in FD (r = -0.459, p = 0.048, uncorrected). Conclusions: In this study, we discovered that FD patients have different perceptual and emotional responses to food intake in defined brain areas, providing promising impetus for understanding pathogenic brain mechanisms in FD.

Prognostic significance of chemokines CCL11 and CCL5 modulated by low-density lipoprotein cholesterol in colon cancer patients with normal body mass index.

BACKGROUND: Many studies have shown an elevated level of cholesterol in colon tumors as compared to normal tissue. Obesity and high low-density lipoprotein cholesterol (LDL-C) are known risk factors for colon cancer. However, the role of LDL-C in colon cancer patients with normal body mass index (BMI) remains elusive. METHODS: Levels of serum cholesterol and oxysterols were quantified by ultra-performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS) from 129 individuals with normal BMI, including 32 with solitary polyp, 36 with multiple polyps, and 31 with adenocarcinoma as well as 32 healthy controls. In vitro, colon cancer cells were treated with LDL-C and assayed for chemokines via RNA-Seq and mitochondrial morphology via transmission electron microscopy and immunofluorescence. Additionally, correlation analysis was performed between LDL-C-induced chemokines and the overall survival of colon cancer patients from the Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression (GTEx), and the Human Protein Atlas (HPA) database. RESULTS: The serum cholesterol level was significantly higher in colon adenocarcinoma patients with normal BMI than that in healthy controls (P<0.001). LDL-C potentiated colon cancer cell invasion and resistance to glucose-deprivation in vitro via chemokine-mediated signaling, mainly upregulation of CC chemokine ligand (CCL) 5 and downregulation of CCL 11. By analyzing the RNA expression data of colorectal cancer from TCGA, GTEx, and HPA, we demonstrated that the CCL5 level in colorectal adenocarcinoma tissues was significantly increased relative to adjacent normal tissues (P=0.01) while the CCL11 level was decreased (P=0.01). Both increased CCL5 and decreased CCL11 showed a negative correlation with the 5-year overall survival in tumor node metastasis (TNM) stage II colon cancer patients (P=0.0032, 0.026 for CCL5 and CCL11, respectively). CONCLUSIONS: Our study supports the idea that LDL-C regulates the expression of CCL5 and CCL11 chemokines, which may have predictive values for survival in colon cancer patients with normal BMI, especially for patients in TNM stage II.

Serum lipid levels correlate to the progression of gastric cancer with neuroendocrine immunophenotypes: A multicenter retrospective study.

PURPOSE: Dyslipidemia was associated with gastric adenocarcinoma or neuroendocrine tumors, but its role in a more malignant entity, gastric cancer with neuroendocrine immunophenotypes (GCNEI), was unclarified. This study sought to explore the relationship between serum lipid levels and the biological behaviors of gastric cancer with neuroendocrine immunophenotypes (GCNEI). METHODS: Patients with neuroendocrine carcinoma (NEC), GC with NEC components (GC-NEC), or GC expressing NE marker(s) but no NE morphology (GC-NENM) were enrolled from three centers. Their preoperative serum lipid levels, demographic, and clinicopathological information were analyzed and compared with those of patients with pure adenocarcinoma (PAC) or a background population selected from 10,061 health-check people by propensity-score matching. RESULTS: A total of 342 GCNEI patients were enrolled. Compared with the background population, total cholesterol (TCHO) and high-density lipoprotein cholesterol (HDL-C) levels were lower in GCNEI. Compared with PAC, GC-NENM and GC-NEC showed lower triglyceride (TG) levels, while, carcinoma with NE morphology showed higher low-density lipoprotein cholesterol (LDL-C) levels. Among GCNEI subtypes, GC-NEC differed from the others by higher LDL-C and non-HDL-C levels. A higher LDL-C level and(or) lower TG, HDL-C levels correlated to higher stages or large tumor sizes in GC-NENM, and a lower HDL-C level correlated to large tumor sizes in GC-NEC. A higher LDL-C level, lower TG, HDL-C, and non-HDL levels increased the risk of GC-NEC, and lower TG, and HDL-C levels increased the risk of GC-NENM and NEC. CONCLUSION: GCNEI had distinct and heterogeneous serum lipid patterns, which correlated to tumor development and progression.

Risk factors of tumor invasion and node metastasis in early gastric cancer with undifferentiated component: a multicenter retrospective study on biopsy specimens and clinical data.

BACKGROUND: Early gastric cancer (EGC) with undifferentiated component (UDC) is a more aggressive entity, where the significance of preoperative data to tumor invasion and lymph node metastasis (LNM) remains unclarified. METHODS: A total of 5,020 GC patients undergoing radical gastrectomy in three centers were reviewed, of which, EGC with UDC in preoperative biopsy specimens were enrolled. The histology of biopsy and surgical specimens was graded according to the proportion of UDC and signet ring cells (SRCs). Risk factors of tumor invasion and LNM were evaluated with histological, clinical and demographic data. RESULTS: Lower body mass index (BMI), melena and larger tumor size were the independent preoperative risk factors of both LNM and LVI, while ulcerative lesion (UL) and the lower third stomach were only correlated with LNM. No relevance was found between the histological features of biopsy specimens and LNM, but SRC or >50% UDC lowered the risk of lymphovascular invasion (LVI) and/or submucosal (SM) invasion. When surgical data (depth of invasion and LVI included) were added, lower BMI, melena and the lower third stomach were still the independent preoperative risk factors of LNM, and LVI, SRC and SM invasion also showed relevance to LNM. The performance of predictive models using pre- or postoperative histological data was comparable. CONCLUSIONS: The preoperative data were significantly relevant to tumor invasion and LNM, showing comparable risk strength with surgical specimens in histology.

Inhibition of DNA­PK by gefitinib causes synergism between gefitinib and cisplatin in NSCLC.

Lung cancer has the highest incidence and mortality rates among the malignant tumor types worldwide. Platinum­based chemotherapy is the main treatment for advanced non­small­cell lung cancer (NSCLC), and epidermal growth factor receptor­tyrosine kinase inhibitors (EGFR­TKIs) have greatly improved the survival of patients with EGFR­sensitive mutations. However, there is no standard therapy for treating patients who are EGFR­TKI resistant. Combining EGFR­TKIs and platinum­based chemotherapy is the most popular strategy in the clinical practice. However, the synergistic mechanism between EGFR­TKIs and platinum remains unknown. Therefore, the aim of the present study was to determine the synergistic mechanism of gefitinib (an EGFR­TKI) and cisplatin (a main platinum­based drug). MTT assay, apoptosis analysis, tumorsphere formation and an orthotropic xenograft mouse model were used to examine the combination effects of gefitinib and cisplatin on NSCLC. Co­immunoprecipitation and immunofluorescence were used to identify the underlying mechanism. It was found that gefitinib could selectively inhibit EGFR from entering the nucleus, decrease DNA­PK activity and enhance the cytotoxicity of cisplatin on NSCLC. Collectively, the results suggested that inhibition of DNA­dependent protein kinase by gefitinib may be due to the synergistic mechanism between gefitinib and cisplatin. Thus, the present study provides a novel insight into potential biomarkers for the selection of combination therapy of gefitinib and cisplatin.

PARK2 Suppresses Proliferation and Tumorigenicity in Non-small Cell Lung Cancer.

Aims: PARK2 mutation is originally associated with the progression of Parkinson's disease. In recent years, PARK2 has been reported as a tumor suppressor gene in various cancers, including lung cancer. However, the biological functions and potential molecular mechanisms of PARK2 in non-small cell lung cancer (NSCLC) are still unclear. Methods: The level of PARK2 expression in 32 tissue samples of NSCLC and matched non-tumor lung tissues was detected by Western blot, and 64 specimens of NSCLC tissues were detected by immunohistochemistry. H1299 and H460 cell lines were used to PARK2 overexpression models, and H460 cell line was also used to PARK2 knockdown model. Using cell viability, colony formation, cell cycle, apoptosis, migration, and invasion assay, the biological functions of PARK2 were evaluated and the potential molecular mechanism of PARK2 was investigated in vitro. Meanwhile, 22 nude mice were employed for in vivo studies. Results: Western blot analysis revealed a decrease of PARK2 protein expression in human NSCLC samples. Immunohistochemistry also identified a vastly reduced expression of PARK2 in NSCLC (72%) and low PARK2 expression was significantly associated with tumor histological grade, lymph node metastasis and advanced TNM stage. Overexpression of PARK2 suppressed cell proliferation, colony formation, migration, and invasion, arrested cell cycle progression in the G1 phase, and induced apoptosis in human non-small cell lines H1299 and H460 in vitro. Meanwhile, knockdown of PARK2 had the opposite biological functions. In addition, PARK2 significantly decreased the tumor volumes in subcutaneous xenograft model and reduced the incidence of metastatic tumors in the transfer model. Exploration of the molecular mechanism of PARK2 in NSCLC showed that PARK2 negatively regulated the EGFR/AKT/mTOR signaling pathway. Conclusions: PARK2 was an important tumor suppressor in NSCLC, which might inhibit cancer growth and metastases through the down regulation of the EGFR/AKT/mTOR signaling pathway.

Elevated level of mitochondrial reactive oxygen species via fatty acid ß-oxidation in cancer stem cells promotes cancer metastasis by inducing epithelial-mesenchymal transition.

BACKGROUND: Cancer stem cells (CSCs) play a critical role in tumor development and progression and are involved in cancer metastasis. The role of reactive oxygen species (ROS) in CSCs and cancer metastasis remains controversial. The aim of the present study was to investigate the correlation between ROS level of CSCs and cancer metastasis and to explore the possible underlying molecular mechanisms. METHODS: Four different cell lines were used to isolate tumor spheres and to analyze intrinsic properties of tumor sphere cells including proliferation, self-renewal potential, differentiation, drug-resistance and cancer metastasis in vitro and in vivo. ROS assays were used to detect the intracellular ROS level of tumor spheres cells. Gene expression analysis and western blot were used to investigate the underlying mechanisms of ROS in regulating cancer metastasis. RESULTS: Tumor spheres possessed the characteristic features of CSCs, and ROS-high tumor spheres (RH-TS) displayed elevated mitochondrial ROS level exclusively drove metastasis formation. The gene expression analysis showed elevated fatty acid ß-oxidation, downregulation of epithelial marker upregulation of mesenchymal markers, and the activation of MAP kinase cascades. Furthermore, 14 up-regulated genes in RH-TS cells were associated with reduced overall survival of different cancer patients. CONCLUSIONS: Our findings demonstrate that CSCs characterized by elevated mitochondrial ROS level potentiate cancer metastasis. Mechanistically, elevated mitochondrial ROS via fatty acid ß-oxidation, activates the MAPK cascades, resulting in the epithelial-mesenchymal transition (EMT) process of RH-TS cells, thereby potentiating caner invasion and metastasis. Therefore, targeting mitochondrial ROS might provide a promising approach to prevent and alleviate cancer metastasis induced by RH-TS cells.

Ursolic acid synergistically enhances the therapeutic effects of oxaliplatin in colorectal cancer.

Oxaliplatin is a key drug in chemotherapy of colorectal cancer (CRC). However, its efficacy is unsatisfied due to drug resistance of cancer cells. In this study, we tested whether a natural agent, ursolic acid, was able to enhance the efficacy of oxaliplatin for CRC. Four CRC cell lines including SW480, SW620, LoVo, and RKO were used as in vitro models, and a SW620 xenograft mouse model was used in further in vivo study. We found that ursolic acid inhibited proliferation and induced apoptosis of all four cells and enhanced the cytotoxicity of oxaliplatin. This effect was associated with down-regulation of Bcl-xL, Bcl-2, survivin, activation of caspase-3, 8, 9, and inhibition of KRAS expression and BRAF, MEK1/2, ERK1/2, p-38, JNK, AKT, IKKα, IκBα, and p65 phosphorylation of the MAPK, PI3K/AKT, and NF-κB signaling pathways. The two agents also showed synergistic effects against tumor growth in vivo. In addition, ursolic acid restored liver function and body weight of the mice treated with oxaliplatin. Thus, we concluded that ursolic acid could enhance the therapeutic effects of oxaliplatin against CRC both in vitro and in vivo, which offers an effective strategy to minimize the burden of oxaliplatin-induced adverse events and provides the groundwork for a new clinical strategy to treat CRC.

Calibrated automated thrombography for monitoring coagulation function in patients with intracerebral haemorrhage.

OBJECTIVE: To monitor coagulation function in patients with intracerebral haemorrhage (ICH) using calibrated automated thrombography. METHODS: Patients admitted to hospital with ICH (confirmed within 18 h of symptom onset) were enrolled. Patient history and blood samples were obtained within 6 h of admission; further blood samples were collected on days 4, 8 and 15 (or on discharge between days 9-15: grouped with day 15 data). Blood samples were also collected from age- and sex-matched healthy controls. All samples underwent calibrated automated thrombography. RESULTS: At admission, thrombin lag time and time to peak was longer, and endogenous thrombin potential and peak height were lower, in patients with ICH (n = 20) than in healthy controls (n = 29). Lag time in patients with ICH gradually decreased, but remained significantly longer than in controls until day 8. Time to peak also gradually decreased, but remained longer in patients than in controls by day 15. Endogenous thrombin potential and peak height gradually increased in patients, but remained lower than in controls on day 15. CONCLUSIONS: Patients with ICH have poorer coagulation function than healthy individuals, but this function gradually recovers during hospitalization.

The clinical effect of deferoxamine mesylate on edema after intracerebral hemorrhage.

BACKGROUND AND PURPOSE: It has been shown that 3 days of 62 mg/kg/day deferoxamine infusion (maximum dose not to exceed 6000 mg/day) is safe and tolerated by intracerebral hemorrhage (ICH) patients. The aim of this study was to investigate the efficacy of deferoxamine mesylate for edema resolution and hematoma absorption after ICH. METHODS: From February 2013 to May 2014, spontaneous ICH patients diagnosed by computed tomography (CT) within 18 hours of onset were evaluated. Patients were randomly divided into two groups: an experimental group and a control group. The treatment of the two groups was similar except that the experimental group received deferoxamine mesylate. Patients were evaluated by CT and neurology scale at the time of admission, and on the fourth, eighth, and fifteenth day (or at discharge) after admission. Patients were followed up for the first 30 days and clinical data of the two groups were compared. RESULTS: Forty-two patients completed 30 days of follow-up by May 2014; 21 cases in the experimental group and 21 cases in the control group. The control group's relative edema volume on the fifteenth day (or discharge) was 10.26 ± 17.54, which was higher than the experimental group (1.91 ± 1.94; P < 0.05). The control group's 1-8 day and 8-15 day relative hematoma absorption were greater than the experimental group (P < 0.05).The control group's relative edema volume on the fourth, eighth, and fifteenth day (or discharge) was higher than the experimental group (P < 0.05). Neurological scores between the two groups were not statistically different on the fifteenth day (or discharge) or on the thirtieth day. CONCLUSIONS: Deferoxamine mesylate may slow hematoma absorption and inhibit edema after ICH, although further investigation is required to form definitive conclusions. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-TRC-14004979.