Case Report: A novel TP53 mutation in a patient with quadruple wild-type gastrointestinal stromal tumor.

In this report, we present a case study of a 64-year-old female who was diagnosed with gastrointestinal stromal tumors (GISTs) and subsequently developed liver metastases despite undergoing radical resection. Next-generation sequencing (NGS) assays indicated that the tumor lacked KIT/PDGFRA/SDH/RAS-P (RAS pathways, RAS-P) mutations, thereby classifying this patient as quadruple WT GIST (qGIST). Treatment with imatinib was initiated, and after 2.5 months, recurrence of the tumor and multiple metastases around the surgical site were observed. Consequently, the patient was switched to sunitinib treatment and responded well. Although she responded well to sunitinib, the patient died of tumor dissemination within 4 months. This case study highlights the potential efficacy of imatinib and the VEGFR-TKI sunitinib in treating qGIST patients harboring a TP53 missense mutation.

The Performance Investigation of Smart Diagnosis for Bearings Using Mixed Chaotic Features with Fractional Order.

This article presents a performance investigation of a fault detection approach for bearings using different chaotic features with fractional order, where the five different chaotic features and three combinations are clearly described, and the detection achievement is organized. In the architecture of the method, a fractional order chaotic system is first applied to produce a chaotic map of the original vibration signal in the chaotic domain, where small changes in the signal with different bearing statuses might be present; then, a 3D feature map can be obtained. Second, five different features, combination methods, and corresponding extraction functions are introduced. In the third action, the correlation functions of extension theory used to construct the classical domain and joint fields are applied to further define the ranges belonging to different bearing statuses. Finally, testing data are fed into the detection system to verify the performance. The experimental results show that the proposed different chaotic features perform well in the detection of bearings with 7 and 21 mil diameters, and an average accuracy rate of 94.4% was achieved in all cases.

GRIK5 stimulates colon cancer growth and metastasis through cAMP/PKA/CADM3 signaling.

Glutamate receptor, ionotropic, kainate 5 (GRIK5) is a member of glutamate receptors participating, and the kainate receptor family has been proved to regulate cell proliferation and transformation. Our study aimed at exploring the role of GRIK5 in colon tumor progression. Three hundred and ninety eight colon cancer patients in The Cancer Genome Atlas Program (TCGA) data set and 26 clinical colon cancer patients were included for GRIK5 expression and prognosis analysis. GRIK5 overexpressed HCT116 and CT26 cell lines were established for cell proliferation and Transwell assay. Western blot analysis and immunostaining assay was conducted to evaluate the activation of activation of cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/cell adhesion molecular 3 (CADM3) signaling in cell lines and tumor tissues. Subcutaneous CT26-bearing mice model was established to examine GRIK5-induced tumor growth and metastasis in vivo. Our study identified GRIK5 to be upregulated in patients with colon cancer, and higher GRIK5 levels correlated with the poor overall survival in patients. In vitro, GRIK5 overexpression markedly enhanced the proliferative properties and aggressive behaviors of colon cancer cells. Mechanistically, GRIK5 induced the activation of cAMP/PKA signaling, proceeded with augmented CADM3 expression, eventually resulting in sustained tumor growth. GRIK5 was a crucial scaffold in enabling colon cancer growth and metastasis, which offered a promising target for therapeutic manipulation of colon cancer.

Dissolved organic matter-assisted phytoremediation potential of cotton for Cd-contaminated soil: a relationship between dosage and phytoremediation efficiency.

Dissolved organic matter (DOM) is a novel Cd-contaminated soils amendment for phytoremediation. However, the phytoremediation efficiency for different DOM doses has been insufficiently investigated. In this study, we investigated the effect of five DOM doses (v/w, 0%, 1%, 2%, 4% and 8%) on the phytoremediation efficiency of cotton in Cd-contaminated soil through pot experiment. The results showed that bioavailable Cd concentrations and organic matter in the soil increased with the increased of DOM dosage. The DOM dose increased the chlorophyll content, photosynthesis, and the total biomass of cotton. In addition, the DOM application increased the Cd content in cotton roots and changed the Cd uptake in cotton shoots, increasing shoot Cd extraction efficiency by 8.53-20%. Simultaneously, soil Cd phytoextraction efficiency significantly increased. Furthermore, applying a 1% DOM dose resulted in safeguarding fibre biomass and maximising the efficiency of shoot extraction. Redundancy analysis showed that the Mn content in leaves is critical for increasing cotton biomass, anti-oxidation competence and phytoremediation efficiency under 1% DOM dose. In conclusion, DOM enhanced cotton remediation in Cd-contaminated soils and applying DOM at 1% was a suitable choice for Cd-contaminated soils.

[Aerobic Granulation Stability and Microbial Diversity of Filamentous Bulking Sludge].

Filamentous bacteria, as one of the common bacteria types in wastewater biological treatment, are considered to be the main factor to induce sludge bulking. However, because of its special filamentous shape, it plays a crucial role in the formation of sludge particles. Taking filamentous bulking sludge as the research object, the effect of filamentous bacteria on the sludge granulation process and maintaining the stability of sludge granules was studied, and the microbial diversity of the sludge system was analyzed. Filamentous bulking sludge (SVI=241.56 mL·g-1) and flocculated sludge (SVI=64.22 mL·g-1) were respectively inoculated to carry out granulation culture. The results showed that the time of particle appearance of bulking sludge and flocculated sludge was 20 days and 40 days, respectively; the mature particle sizes were 650 µm and 700 µm, respectively; and the granulation time of bulking sludge was only half that of flocculated sludge. After adding the anoxic zone, the granules were broken to differing degrees, but the SV30/SV5 value of mature granules recovered to 1 after short-term fluctuation, and the stability of the mature granules was stronger. The analysis of microbial community structure showed that the relative abundance of norank_o__Saccharimonadales, unclassified_o__Saccharimonadales, and unclassified_f__Saccharimonadaceae increased from 0.05%, 0.01%, and 0.01% to 4.09%, 3.15%, and 1.12%. The existence and accumulations of these hydrophobic bacteria were important for rapid granulation. The removal rates of COD, NH4+-N, and TN were 94%, 99%, and 35% and 92%, 97%, and 30%, respectively, in SBR1 of bulking sludge and SBR2 of flocculated sludge, and the removal rates of TP were 60% and 30%, respectively.

Effect of dissolved organic matter on the phytoremediation of Cd-contaminated soil by cotton.

Dissolved organic matter (DOM) assists in the phytoremediation of heavy-metal-contaminated soils, but the effect of synergistic remediation of DOM on plants is unclear. This study investigated the effect of two DOM sources (cotton straw (CM) DOM and farmyard manure (FM) DOM) on cadmium (Cd) accumulation in Cd-contaminated soil by cotton and evaluated the phytoremediation effect of DOM. The results showed that adding DOM reduced the available nitrogen and increased organic matter, available phosphorus and available potassium. Applying DOM increased the proportions of Cd acid soluble fractions and reduced the proportions of Cd residual fractions by 1-7%. DOM application increased root length, root surface area and root volume compared to the control and had a promoting or inhibiting effect on cotton biomass, depending on the soil Cd concentration. Furthermore, applying DOM improved the Cd content and bioconcentration factor of cotton. The lower the molecular weight, hydrophilic components and aromaticity of DOM, the more conducive to Cd accumulation is in cotton. The correlation and random forest analyses also showed that CM showed high remediation potential. According to our study, DOM can improve the phytoremediation efficiency of cotton, especially in low-concentration contaminated soils. This study provides a basis for applying DOM in the phytoremediation of Cd-contaminated soils.

Prevalence and Spectrum of Predisposition Genes With Germline Mutations Among Chinese Patients With Bowel Cancer.

Background: Bowel cancer is the third-most common cancer and the second leading cause of cancer-related death worldwide. Bowel cancer has a substantial hereditary component; however, additional hereditary risk factors involved in bowel cancer pathogenesis have not been systematically defined. Materials and Methods: A total of 573 patients with bowel cancer were enrolled in the present study, of whom 93.72% had colorectal cancer (CRC). Germline mutations were integrated with somatic mutation information via utilizing target next-generation sequencing. Results: Pathogenic/Likely Pathogenic (P/LP) germline alterations were identified in 47 (8.2%) patients with bowel cancer and the ratio of the number of these patients with family history was significantly higher in the P/LP group than that noted in the non-pathogenic (Non-P) group. Certain rare germline alterations were noted, such as those noted in the following genes: FANCD2, CDH1, and FLCN. A total of 32 patients (68.1%) had germline alterations in the DNA-damage repair (DDR) genes and homologous recombination (HR) accounted for the highest proportion of this subgroup. By comparing 573 patients with bowel cancer with reference controls (China_MAPs database), significant associations (p < 0.01) were observed between the incidence of bowel cancer and the presence of mutations in APC, ATM, MLH1, FANCD2, MSH3, MSH6, PMS1, and RAD51D. Somatic gene differential analysis revealed a marked difference in 18 genes and a significant difference was also noted in tumor mutation burden (TMB) between germline mutation carriers and non-germline mutation subjects (p < 0.001). In addition, TMB in DDR mutation groups indicated a dramatic difference compared with the non-DDR mutation group (p < 0.01). However, no statistically significant differences in TMB were noted among detailed DDR pathways for patients with bowel cancer, irrespective of the presence of germline mutations. Moreover, a significantly higher level (p < 0.0001) of mutation count was observed in the DDR group from The Cancer Genome Atlas (TCGA) database and the DDR and non-DDR alteration groups displayed various immune profiles. Conclusion: Chinese patients with bowel cancer exhibited a distinct spectrum of germline variants, with distinct molecular characteristics such as TMB and DDR. Furthermore, the information on somatic mutations obtained from TCGA database indicated that a deeper understanding of the interactions among DDR and immune cells would be useful to further investigate the role of DDR in bowel cancer.

Comparative study of two cephalosporin antibiotics binding to calf thymus DNA by multispectroscopy, electrochemistry, and molecular docking.

The over-use of antibiotics has caused a number of problems such as contamination of antibiotic residues and virus resistance, and therefore has attracted global attention. In this study, spectroscopic techniques and molecular docking were employed to predict conformational changes and binding interaction between two cephalosporins (cefaclor and cefixime) and calf thymus DNA (ctDNA). Fluorescence and UV-vis spectra suggested that static quenching was predominant and cephalosporin bound to the groove region of ctDNA. Binding parameters calculated by the Stern-Volmer and Scatchard equations showed that cephalosporin bound to ctDNA with a binding affinity in the order of 103  L mol-1 . Thermodynamic parameters further indicated that the reaction was a spontaneous process driven by enthalpy and entropy, and that the main binding force was an electrostatic force. The effects of iodide, denaturant, thermal denaturation and pH on a cephalosporin-Hoechst-DNA complex were also studied, and the results confirmed that cephalosporin bound to the groove area of DNA. Finally, these results were further confirmed by molecular docking and electrochemical studies.

Probing the interaction of cephalosporin with bovine serum albumin: A structural and comparative perspective.

Cephalosporins belong the largest class of antibiotics used in the treatment of a wide range of infectious diseases caused by susceptible organisms. In the present study, we chose two typical antibiotics cefalexin/cefixime based on their structure, and investigated the interaction of cephalexin/cefixime with bovine serum albumin (BSA) using UV-vis absorption spectra, fluorescence spectroscopy, circular dichroism (CD) spectroscopy and molecular modeling approaches. Spectroscopic experiments revealed the formation of a BSA - cefalexin/cefixime complex. The binding parameters calculated using a modified Stern - Volmer method and the Scatchard method reached 103 -104  L·mol-1 . Thermodynamic parameter studies revealed that binding characteristics by negative enthalpy and positive entropy changes, and electrostatic interactions play a major role. Site marker competitive displacement experiments and molecular modeling approaches demonstrated that cefalexin and cefixime bind with appropriate affinity to site I (subdomain IIA) of BSA. Furthermore, synchronous fluorescence spectra, CD spectra and molecular modeling results indicated that the secondary structure of BSA was changed in the presence of cefalexin and cefixime. Additionally, the effects of metal ions on the BSA - cefalexin/cefixime system were also assessed.

Insights into the interaction of methotrexate and human serum albumin: A spectroscopic and molecular modeling approach.

In this study, fluorescence spectroscopy and molecular modeling approaches were employed to investigate the binding of methotrexate to human serum albumin (HSA) under physiological conditions. From the mechanism, it was demonstrated that fluorescence quenching of HSA by methotrexate results from the formation of a methotrexate/HSA complex. Binding parameters calculated using the Stern-Volmer method and the Scatchard method showed that methotrexate binds to HSA with binding affinities in the order 104  L·mol-1 . Thermodynamic parameter studies revealed that the binding reaction is spontaneous, and that hydrogen bonds and van der Waals interactions play a major role in the reaction. Site marker competitive displacement experiments and a molecular modeling approach demonstrated that methotrexate binds with appropriate affinity to site I (subdomain IIA) of HSA. Furthermore, we discuss some factors that influence methotrexate binding to HSA.

[Impact of preoperative oral liquid carbohydrate on postoperative insulin resistance in gastric cancer patients and its associated study].

OBJECTIVE: To investigate the impact of preoperative oral liquid carbohydrate on postoperative insulin resistance (IR) in gastric cancer patients undergoing elective resection, and to examine the association of IR index (homeostasis model assessment, HOMA-IR) with tumor necrosis factor-α (TNF-α). METHODS: Between January 2013 and September 2013, 35 patients undergoing elective resection for gastric cancer were prospectively enrolled and randomized into two groups. Patients in trial group (n=18) received oral 500 ml of 10% glucose solution two hours before surgery. Patients in control group (n=17) were asked to fast for 8-12 hours before operation. About 300 mg of rectus abdominis and subcutaneous fatty tissues was removed before the closure of abdominal wall. Blood samples were collected to measure the serum concentration of TNF-α with double antibody sandwich ELISA in perioperative period (3-hour before operation, end of operation, 1-day and 3-day after operation). HOMA-IR was calculated on preoperative 3-hour and postoperative 1-day. Western blotting was used to detect protein expression of TNF-α. Correlation of HOMA-IR with TNF-α was examined. RESULTS: HOMA-IR on the first day after surgery was not different from that at 3-hour before surgery in trial group (P=0.090), which was significantly lower than that in control group (P=0.000). In trial group, serum TNF-α at the end of operation was higher than that at 3-hour before surgery, which declined rapidly on the first day after surgery and had no significant difference compared with that on the third day after surgery. In control group, serum TNF-α at the end of operation was also higher than that before surgery, which rose to the peak on the first day after surgery and was still higher than that at 3-hour before surgery. The TNF-α protein expression in muscle tissues of trial group was higher than that of control group (P=0.001), while no significant difference was observed between two groups in adipose tissues (P=0.987). Correlation analysis showed that HOMA-IR was positively correlated with TNF-α on the first day after surgery (r=0.832, P=0.000). CONCLUSION: Oral intake of liquid carbohydrate 2 hours before surgery can reduce the level of TNF-α, which is likely to improve the postoperative insulin resistance.

Paired design study by real-time PCR: miR-378* and miR-145 are potent early diagnostic biomarkers of human colorectal cancer.

BACKGROUND: Although microRNAs offer great potential as cancer biomarkers, effective clinical dignostics and tumor maker have not been verified to diagnose with colorectal cancer (CRC). The purpose of our study is to systematically assess the expression of miRNAs in matched cancer and normal tissue samples to identify promising diagnostic microRNA (miRNA) biomarkers for CRC. METHODS: In our study, we examined by Real-Time PCR the expression levels of 96 mature miRNA in 32 CRC patients with differently expressed tumors versus normal colon tissues. Using enter and stepwise variable selection methods separately, conditional logistic regression was conducted to identify miRNAs associated with CRC. The classification performance of these indicators was assessed under the Fisher discriminant analysis. Receiver operating characteristic curve analyses were applied to obtain diagnostic utility of the differentially expressed miRNAs. RESULTS: In this study, we confirmed 11 overexpressed miRNAs with no less than twofold difference, and 85 downexpressed miRNAs with up to 0.5-fold difference in CRC from 96 aberrantly expressed miRNAs being identified by real-time PCR. Conditional logistic regression results confirmed that miRNA-378 and miRNA-145 expression profile was statistically significant. The error diagnosis rate of these two miRNAs are 0.194 and 0.113, separeately, showing by discriminant analysis. CONCLUSIONS: MiRNA-145 and miRNA-378* are potential biomarkers for early detection of CRC, which may help in diagnosing CRC in early period.

Novel rare earth tungstoarsenate heteropolyoxometalates K11[Ln(AsW 11O 39) 2]·xH 2O (Ln = La, Nd, Sm) binding to bovine serum albumin: spectroscopic approach.

The rare earth salts of heteropoly have been widely applied in many fields. In this study, the biological activity of rare earth tungstoarsenate heteropolyoxometalates K11[Ln(AsW11O39)2]·xH2O (abbr. LnW11, Ln = La (x = 24), Nd (x = 17), and Sm (x = 19)) were investigated by spectroscopic methods including fluorescence spectroscopy and UV-vis absorption spectroscopy at different temperatures. In the mechanism discussion, it was proved that the fluorescence quenching of bovine serum albumin (BSA) by LnW11 is initiated by complex formation. The thermodynamic parameters suggested that the binding of LnW11 to BSA is spontaneous, and the mainly force is electrostatic interactions. Site marker competitive experiments demonstrated that LaW11 binds with high affinity to site I (subdomain IIA) of BSA; but SmW11 and NdW11 bind with affinity to both site I (subdomain IIA) and site II (subdomain IIIA) of BSA. The results of synchronous fluorescence spectrum indicate that the secondary structure of BSA molecules was changed in the presence of LnW11. In addition, the binding parameters, binding site number, and effect of metal ions on LnW11-BSA were also discussed.

[Preliminary experiences of application of sentinel lymph node navigation technique in early gastric cancer].

OBJECTIVE: To investigate the feasibility and clinical significance of sentinel lymph node (SLN) navigation limited surgery in early gastric cancer (EGC). METHODS: Thirty-nine patients confirmed with EGC between January 2002 and December 2006 were randomly divided into tailored surgery group (20 cases) and conventional surgery group (19 cases). By combining the mapping agents of (99m)Tc labeled sulfur colloid solution and blue violet, SLN biopsy was conducted in tailored surgery group, in which a limited gastric resection with D0-D1 lymphadenectomy was performed in 17 cases with negative SLN examined by routine HE staining during operation; standard radical gastrectomy with lymphadenectomy (D2) was conducted in the other 3 cases with positive SLN and in all the cases of conventional surgery group. The diagnostic accuracy and false-negative rate of SLN status were calculated respectively. The operation outcome and postoperative complication and survival rate were compared between the two groups. RESULTS: SLNs were detected in all 20 patients with a successful detection rate of 100% in tailored surgery group. The number of detected SLNs ranged from 1 to 3, with a mean of 2.2 per case. The diagnostic accuracy and false-negative rate was 95% and 5%, respectively. The hospital stay and recovery time of gastrointestinal functions in patients undergoing limited surgery were significantly shorter than in conventional surgery group and with similar postoperative survival and less complications. CONCLUSIONS: SLN biopsy may provide an accurate diagnostic procedure for detecting lymph node metastasis in EGC. Patients with node-negative EGC receiving limited surgery are likely to benefit from minimally invasive approach with the similar survival as standard radical surgery.

[Clinical significance of sentinel lymph node detection by combining the dye-directed and radioguided methods in gastric cancer].

OBJECTIVE: To investigate the feasibility and accuracy of detection of sentinel lymph nodes (SLN) with combining the dye-directed and radioguided methods in gastric cancer and assess its potential role in determining the rational extent of lymphadenectomy in gastric cancer surgery. METHODS: Twenty-six patients of gastric cancer diagnosed as T(1)-T(3) were enrolled in this study. Endoscopic injection submucosally of (99m)Tc labeled sulfur colloid solution was performed around the primary tumor 2 - 4 h before operation. Immediately after laparotomy, patent blue violet was injected into subserosal layer adjacent to the tumor. SLNs were defined as blue stained nodes or(and) those containing 10 times more radioactivity than surrounding tissue with a gamma probe. Standard radical gastrectomy with lymphadenectomy (D(2) or D(3)) was performed in most of the patients, however, limited surgery was performed in early gastric cancer (EGC) when a rapid frozen examination indicated negative SLNs. All resected nodes were examined postoperatively by routine HE stain and those negative SLNs were examined with further cytokeratin immunohistochemistical staining. The diagnostic accuracy, sensitivity, negative predictive value and false-negative rate of regional lymph node status on the basis of SLN status were calculated respectively. RESULTS: SLNs were dectected in 25 of 26 patients with a successful detection rate of 96%. The number of SLNs ranged from 1 to 6, with a mean value of 3.2 per case. The SLNs of gastric cancer were only found in N(1) area in 50% of the cases, and only in N(2) or N(3) in 12%. The incidence of metastasis was significantly higher in SLNs than in non-SLNs (35% vs 7%). The diagnostic accuracy, sensitivity, negative predictive value and false-negative rate were 96%, 94%, 7/8 and 6% respectively. Complete analysis of SLN upstaged 2/7 of patients of gastric cancer. CONCLUSIONS: The SLN concept is validated in gastric cancer. Combined-agent SLN mapping is an accurate diagnostic procedure for detecting lymph node metastasis in patients with gastric cancer and may indicate rational extent of lymphadenectomy for gastric cancer.

Sentinel lymph node concept in gastric cancer with solitary lymph node metastasis.

AIM: To study the localization of the solitary metastases in relation to the primary gastric cancers and the feasibility of sentinel lymph node (SLN) concept in gastric cancer. METHODS: Eighty-six patients with gastric cancer, who had only one lymph node involved, were regarded retrospectively as patients with a possible sentinel node metastasis, and the distribution of these nodes were assessed. Thirteen cases with jumping metastases were further studied and followed up. RESULTS: The single nodal metastasis was found in the nearest perigastric nodal area in 65.1% (56/86) of the cases and in 19.8% (17/86) of the cases in a fairly remote perigastric area. Out of 19 middle-third gastric cancers, 3 tumors at the lesser or greater curvatures had transverse metastases. There were also 15.1% (13/86) of patients with a jumping metastasis to N2-N3 nodes without N1 involved. Among them, the depth of invasion was mucosal (M) in 1 patient, submucosal (SM) in 2, proper-muscular (MP) in 4, subserosal (SS) in 5, and serosa-exposed (SE) in 1. Five of these patients died of gastric cancer recurrence at the time of this report within 3 years after surgery. CONCLUSION: These results suggest that nodal metastases occur in a random and multidirectional process in gastric cancer and that not every first metastatic node is located in the perigastric region near the primary tumor. The rate of "jumping metastasis" in gastric cancer is much higher than expected, which suggests that the blind examination of the nodal area close to the primary tumor can not be a reliable method to detect the SLN and that a extended lymph node dissection (ELND) should be performed if the preoperative examination indicates submucosal invasion.