Isolation and proteomic profiling of urinary exosomes from patients with colorectal cancer.

Exosomes in the body fluid are effective cell-derived membranous structures transferring various molecules to mediate intercellular communication. The expression of protein in the urinary exosomes from the colorectal cancer (CRC) patients could reflect the characteristics of tumorigenesis. The urinary exosomes with globular membrane structure, the size of 30 ~ 100 nm and positive expression of CD9, CD63 and CD81 were successfully isolated from 9 CRC patients and 3 heathy adults using the density gradient ultracentrifugation. Proteome profiles revealed by label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) indicated that several proteins were differentially expressed among different stages of CRC. Compared with normal controls, 67 proteins in CRC urinary exosomes were upregulated and 74 proteins were downregulated. The bioinformatics analysis revealed the decreased proteins were related to ESCRT III complex disassembly. The CHMP family was further determined to be the hub of interaction network of proteins enriched in ESCRT signaling. The significant decrease of CHMP4A, CHMP4B, CHMP2A, CHMP2B and CHMP1B were respectively found in the total CRC group and distant metastasis group compared with NC group. Moreover, the CEACAM family also showed significant aberrant changes in the urinary exosomes of CRC patients. The CEACAM7 and CEACAM1 were increased in the CRC patients compared with healthy individuals (P < 0.05). Significant changes of proteomic profile could be found in the urinary exosomes in the CRC patients. The differential expressed urinary exosomes derived proteins showed potential usage in diagnosis and prognosis of CRC.

Brain metastasis from colorectal cancer: Treatment, survival, and prognosis.

To investigate the clinical characteristics, survival, prognostic factors, and treatment of brain metastasis (BM) from colorectal cancer (CRC). Twenty-one patients with BM from CRC were retrospectively reviewed. Predictive factors for BM and prognostic factors after the diagnosis of BM were examined by univariate and multivariate COX analysis. The time from the development of extracranial metastases, including lung, bone, and liver, to the occurrence of BM was recorded separately. The median overall survival time was 7 months. In univariate prognostic analysis, median survival with multimodal therapy was better than that with unimodal therapy (10 months vs 3 months, P = .000). In addition, median survival with Karnofsky performance status (KPS) < 70, 1 BM lesion, primary tumor stage of II-III, extracranial lesions < 2, and no extracranial metastasis were much better than the other groups (P < .05 of all). Although there was not a significant difference in median survival between patients receiving combination treatment with bevacizumab and those who did not, treatment with bevacizumab was associated with better survival (10 months vs 5 months, P = .436). The time intervals from bone, liver, and lung metastases to BM were 3, 6.5, and 11 months, respectively. Based on multivariate Cox analysis, KPS and treatment modalities were independent prognosis factors (P = .039 and P = .000, respectively). CRC patients with a high KPS and multimodal treatment have improved survival.

Contamination characteristics, source identification, and source-specific health risks of heavy metal(loid)s in groundwater of an arid oasis region in Northwest China.

Heavy metal(loid)s accumulation in groundwater has posed serious ecological and health concerns worldwide. Source-specific risk apportionment is crucial to prevent and control potential heavy metal(loid)s pollution in groundwater. However, there is very limited comprehensive information on the health risk apportionment for groundwater heavy metal(loid)s in arid regions. Thus, the Zhangye Basin, a typical arid oasis region in Northwest China, was selected to investigate the contamination characteristics, possible pollution sources, and source-specific health risks of groundwater heavy metal(loid)s. The heavy metal pollution index (HPI), the Nemerow index (NI), and the contamination degree (CD) were adopted to assess the pollution level of heavy metal(loid)s; then source-specific health risk was apportioned integrating the absolute principal component scores-multiple linear regression (APCS-MLR) with health risk assessment. Noticeable accumulation of Mn, Fe, and As was observed in this region with especially Fe/As in 12.68%/2.11% of the samples revealing significant enrichment. Approximately 3.5% of the groundwater samples caused moderate or higher pollution level based on the HPI. The APCS-MLR model was more physically applicable for the current research than the positive matrix factorization (PMF) model. Industrial-agricultural activity factor (12.56%) was the major source of non-cancer (infants: 59.15%, children: 64.87%, teens: 64.06%, adults: 64.02%) and cancer risks (infants: 77.36%, children: 77.35%, teens: 77.40%, adults: 77.41%). Industrial-agricultural activities should be given priority to control health risks of heavy metal(loid)s in groundwater. These findings provide fundamental and significant information for mitigating health risks caused by heavy metal(loid)s in groundwater of typical arid oasis regions by controlling priority sources.

Humidity-sensitive irreversible phase transformation of open-framework zinc phosphate and its water-assisted high proton conduction properties.

Open-framework zinc phosphate (NMe4)(ZnP2O8H3) undergoes irreversible phase transformation. Structural transformation with α (NMe4·Zn[HPO4][H2PO4] the low-temperature phase) and ß (NMe4·ZnH3[PO4]2 the high-temperature phase) (Tc = 149 °C) and conduction properties were investigated by single-crystal X-ray diffraction, differential scanning calorimetry, and alternating current (ac) impedance. The open-framework material was sensitive to humidity and ß proton conductivity was higher than 10-2 S cm-1 at room temperature and 98% relative humidity (RH). Given that the high proton conductivity of the open-framework material can compete with that of many advanced proton conductors based on metal-organic frameworks (MOFs), it has broad application prospects in various electrochemical devices.

Comprehensive Probabilistic Health Risk Assessment for Exposure to Arsenic and Cadmium in Groundwater.

Probabilistic health risk assessment has widely been used for more realistic risk analysis of contaminants. However, the existing probabilistic modeling process may be unable to reflect the actual health risks comprehensively. In the present study, the Monte Carlo simulation was employed to assess the probabilistic health risks of exposing to arsenic (As) and cadmium (Cd) in groundwater through ingestion and dermal contact pathways. To systematically evaluate the actual health risks of residents, two scenarios of the probabilistic health risk assessment were proposed: (1) fixed exposure parameters, whereas uncertain metal concentrations, and (2) uncertain exposure parameters and metal concentrations. The results indicated that the mean hazard index (HI) for local residents was mostly accepted (HI < 1), while the non-cancer risk of infants at the 95th percentile under scenario 2 (HI = 1.42) exceeded the safe level of 1, signifying the potential non-cancer risk on infants. Meanwhile, the average total cancer risk (TCR) values were several times greater than the acceptable limit of 1E-06 for all the age groups under both scenarios 1 and 2, reflecting the unacceptable cancer risk. Moreover, sensitivity analysis identified the exposure duration (ED) and concentration factor (CW) were the most relevant parameters that affect the health risk. Overall, the results of this study will be useful for the policy makers in comprehensively understanding the actual health risks of the heavy metal(loids) contamination in groundwater on receptors, as well as setting up suitable groundwater management strategies to guarantee safe water supply and to maintain health for local residents.

Significant diagnostic value of circulating tumour cells in colorectal cancer.

Circulating tumour cells (CTCs) have potential utility in various clinical applications for cancer management. The present study focused on evaluating the diagnostic role of CTCs in colorectal cancer (CRC). A total of 89 blood samples from 59 patients diagnosed with CRC and 30 healthy individuals were collected for CTC detection. The Cyttel method is an improved CTC detection strategy, which combines negative enrichment with immunofluorescence and fluorescence in situ hybridization. This method effectively detected a significant increase in total CTCs in patients with CRC (49/59) compared with those in healthy controls (3/30). A cut-off value of 2 CTCs/3.2 ml blood yielded a sensitivity of 83.05% and a specificity of 100%. Additionally, three traditional serum tumour markers, namely carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9) and CA72-4, were examined by immunoassays. The diagnostic sensitivity of CTCs was much higher than that of CEA, CA19-9 and CA72-4 alone or in combination, particularly in patients with early stage CRC. The combined sensitivity of CTCs and CEA reached 91.53%, which was only slightly lower than the sensitivity of all four markers combined (CTCs + CEA + CA19-9 + CA72-4). CTCs with aneuploidy of chromosome 7 or 8 were carefully distinguished, and the associations among different types of CTCs, clinicopathological characteristics and overall survival were statistically analysed. Total CTCs were revealed to be significantly associated with tumour differentiation and nerve invasion. CTCs were more likely to be detected in poorly differentiated CRC tumours than in well- and moderately-differentiated tumours (P=0.026). Furthermore, to the best of our knowledge, the present study was the first to report that CTCs with multiploidy of chromosome 7 were significantly associated with TNM stage. These CTCs exhibited a high chance of being identified in the peripheral blood of patients with late-stage CRC (stage III-IV; P=0.031). The present study suggests that the combination of CTCs and CEA may serve as an effective potential diagnostic and prognostic indicator in patients with CRC. Detection of CTCs with aneuploidy may have increased specificity in predicting highly malignant and invasive tumours in CRC management.

Effects of different methods of general anesthesia on intraoperative awareness in surgical patients.

The purpose of the study was to investigate the effects of total intravenous anesthesia (TIVA) and combined of intravenous and inhaled anesthesia (CIIA) on intraoperative awareness in surgical patients.A total of 678 patients were recruited in the CIIA group, while TIVA group included 566 patients. The clinical characteristics and the occurrence of intraoperative awareness were compared between the groups. Mini-Mental State Examination, Generalized Anxiety Disorder 7, and Patient Health Questionnaire 9 tests were performed to estimate cognitive and psychological functions of the patients. In addition, logistic regression analysis was applied to identify the risk factors for intraoperative awareness in surgical patients.In CIIA group, 3 patients (0.44%) were confirmed with intraoperative awareness, while 11 patients (1.94%) in TIVA group underwent intraoperative awareness. The occurrence rate of intraoperative awareness was significantly higher in VITA group than that in the CIIA group (P = .029). Awareness classification demonstrated that intraoperative awareness mainly included auditory, tactile, and pain perceptions. Moreover, 4 patients showed distress after operation. Patients with intraoperative awareness exhibited poor performance in cognitive and psychological tests (P < .001 for all). Logistic regression analysis demonstrated that CIIA (odds ratio [OR] = 0.198, 95% confidence interval [CI] = 0.047-0.827), age (OR = 0.951, 95% CI = 0.908-0.997), midazolam application (OR = 0.158, 95% CI = 0.034-0.736), awareness history (OR = 10.131, 95% CI = 2.206-45.517), and duration of surgery (OR = 1.016, 95% CI = 1.001-1.032) were significantly associated with intraoperative awareness.Intraoperative awareness can significantly influence the cognitive and psychological functions of surgical patients. CIIA and midazolam application may lower the risk of intraoperative awareness.

Retrograde laparoscopic resection of left side of the liver: a safe and effective way.

OBJECTIVE: The safety and feasibility of retrograde laparoscopic resection of the left side of the liver. METHODS: Ninety-three laparoscopic left hepatic lobe cases were selected between August 2010 and August 2014 from our institution. A retrospective cohort study was performed between the antegrade partial hepatectomy group (47 cases; dissection from the first porta hepatis to the second) and the retrograde partial hepatectomy group (46 cases; dissection from the second porta hepatis to the first), to compare the length of time needed for resection, the amount of bleeding, post-operative time in the hospital, and the incidence of major complications, such as bile leakage, abdominal abscess, and post-hepatectomy hemorrhage. RESULTS: All of the cases had a successful laparoscopic partial hepatectomy without the need for an intraoperative blood transfusion. Patients were able to ambulate on post-operative day 1 and tolerated a liquid diet on post-operative day 1 or 2. There were no statistical differences of post-operative hospital length of stay or incidence of major complications between the two groups. Both duration of resection and the amount of bleeding were less in the retrograde group than of those in the antegrade group, due to the lower incidence of hepatic vein injury in the retrograde group. CONCLUSION: Occlusion of both the inflow and outflow hepatic vessels combined with retrograde hepatectomy from the second porta hepatis to the first, demonstrated less hemorrhage and lower incidence of hepatic veins injury during laparoscopic partial hepatectomy.