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Objective Colorectal cancer (CRC) is one of the most common malignant tumors in the digestive tract, which accounts for 10% of all the malignant tumors in the world. The aim of this study was to identify key genes and miRNAs in CRC diagnosis, prognosis, and therapy and to further explore the potential molecular mechanisms of CRC. Methods The infiltration and metastasis of neutrophils in primary colorectal cancer tissue and paracancerous tissue were observed by immunohistochemical staining. After inducing N2 neutrophils with TGF-β1 in vitro, exosomes were extracted and sequenced, and then the expression differences of miRNAs were screened by using Agilent miRNA microarrays. The data were imported to the Web CARMA for differential expression analysis. The GO and KEGG enrichment analysis were performed using DIANA-MirPath v3.0 using TargetScan database. And the corresponding targets were imported into Gephi for network analysis. The expression level of differentially expressed miRNA using quantitative real-time polymerase chain reaction (RT-PCR) was validated. Results A total of 2 miRNAs were found to be associated with N2 neutrophils, in which the expression of hsa-miR-4780 was upregulated and the expression of hsa-miR-3938 was downregulated in N2 neutrophils, compared with the neutrophils. In addition, the results of miRNA-targets networks showed that the hsa-mir-3938 and hsa-mir-4780 could regulate TUSC1 and ZNF197. The expression level of hsa-miR-4780 and hsa-miR-3938 wase validated in accordance with the results of RT-PCR. Conclusion The hsa-mir-3938 and hsa-mir-4780 were differentially expressed between N2 neutrophils and neutrophils. Moreover, the regulation of TUSC1 and ZNF197 by these DEmiRNA established the theoretical basis for the mechanism of N2 type neutrophils regulating the invasion and metastasis of CRC cells and provided the potential biomarker for prognosis for clinical treatment of CRC.

Gastric cancer is one of the most common cancers, while the current treatment options for gastric cancer are relatively scarce due to insufficient understanding of molecular characteristics and subtypes of gastric cancer. Different gene rearrangements of anaplastic lymphocyte kinase (ALK) have been reported in several types of cancer, especially in NSCLC. The first-generation ALK tyrosine kinase inhibitor (TKI) crizotinib, second-generation (ceritinib, alectinib, and brigatinib) and third-generation (lorlatinib) ALK-TKIs have been widely used for NSCLC patients with ALK rearrangement. However, little was reported about ALK mutation in gastric cancer (GC). Here we identified a novel form of ALK fusion, a case of GC with RAB10-ALK fusion, and this is the first report of ALK fusion in gastric cancer.

Currently, the main treatment for familial adenomatous polyposis (FAP) is surgery, however, surgery is far from ideal as there are many complications such as uncontrollable bowel movements, pouch inflammation, anastomotic stricture, and secondary fibroids. Therefore, it is necessary to further expand the understanding of FAP and develop new treatments for FAP. The immune microenvironment including immune cells and cytokines, plays an important role in FAP and the progression of FAP to adenocarcinoma, thus it may be a promising treatment for FAP. In the current review, we summarized the recent progress in the immune microenvironment of FAP.

Objective: Colorectal cancer (CRC) is one of the most common malignant tumors in the digestive tract, which accounts for 10% of all the malignant tumors in the world. The aim of this study was to identify key genes and miRNAs in CRC diagnosis, prognosis, and therapy and to further explore the potential molecular mechanisms of CRC.Methods: The infiltration and metastasis of neutrophils in Primary colorectal cancer tissue and Paracancerous tissue were observed by immunohistochemical staining. After inducing N2 neutrophils with TGF-β1 in vitro, exosomes were extracted and sequenced, and then the expression differences of microRNAs were screened by using Agilent microRNA microarrays. The data were imported to the Web CARMA for differential expression analysis. The GO and KEGG enrichment analysis were performed using DIANA-MirPath v3.0 using Targetscan database. And the corresponding targets were imported into Gephi for network analysis. The expression level of differentially expressed microRNA using quantitative Realtime polymerase chain reaction (RT-PCR) was validated.Results: A total of 2 miRNAs were found to be associated with N2 neutrophils, in which the expression of hsa-miR-4780 was upregulated and the expression of hsa-miR-3938 was downregulated in N2 neutrophils, compared with the neutrophils. In addition, the results of miRNA-targets networks showed that the hsa-mir-3938 and hsa-mir-4780 could regulate TUSC1 and ZNF197. The expression level of hsa-miR-4780 and hsa-miR-3938 were validated in accordance with the results of RT-PCR.Conclusion: The hsa-mir-3938 and hsa-mir-4780 were differentially expressed between N2 neutrophils and neutrophils. Moreover, the regulation of TUSC1 and ZNF197 by these DEmiRNA established the theoretical basis for the mechanism of N2 type neutrophils regulating the invasion and metastasis of CRC cells, and provided the potential biomarker for prognosis for clinical treatment of CRC

Rationale: Patients with gastrointestinal stromal tumors (GISTs) are often found to have liver metastases at their 1st presentation. Most patients need preoperative treatment to reduce the size of the liver metastases to increase the possibility of surgical resection. Currently, imatinib mesylate is the drug of 1st choice for preoperative treatment and sunitinib malate (SM) is seldom used. Here we report a case of GIST with liver metastases where SM was used as a preoperative treatment. Patient concerns: A 56-year-old worker presented with intermittent abdominal pain and eating difficulties. Diagnoses: An enhanced computed tomography scan showed a 15 × 15 × 10 cm malignant mass in the upper abdomen, and 2 metastases (15.1 × 13.1 cm and 14.8 × 8.8 cm) in the liver. The postcaval and middle hepatic veins were compressed by the liver metastases, making radical resection very difficult. Interventions: First the primary tumor in the jejunum was resected, and then SM was used as a preoperative treatment to reduce the size of the liver metastases to improve the possibility of surgical resection. Outcomes: Both liver metastases regressed considerably in size and it was then possible to perform a radical resection. Lessons: The SM has the potential to be used as preoperative therapy for GIST with large liver metastases. This method provides a new option for the preoperative treatment of GIST with liver metastases.

A new coumarin, anisucoumaramide (1), and a new δ-truxinate derivative, anisumic acid (2), were isolated from Clausena anisum-olens. Their structures were elucidated from extensive NMR and MS data. The absolute configurations of the coumarins were assigned using the experimental and calculated electronic circular dichroism data. Anisucoumaramide (1) represents the first example of a naturally occurring coumarin of which the terpenoidal side chain does not comply with the biosynthesis isoprene rule due to the presence of an unprecedented acetamido motif directly connected with the terpenoidal side chain. The δ-truxinate derivative was isolated from Clausena species for the first time. Compound 1 showed high selectivity for the MAO-B isoenzyme and inhibitory activity in the nanomolar range. Putative biosynthesis pathways toward 1 and 2 are proposed.

The genus Litsea is one of the most diverse genera of evergreen trees or shrubs belong to Lauraceae, and comprises roughly 400 species of tree that are distributed abundantly throughout tropical and subtropical Asia, North and South America. Litsea species have been used globally in traditional medicine for the treatment of various diseases including influenza, stomach aches, diarrhea, diabetes, vomiting, bone pain, inflammation, illness related to the central nervous system and other ailments. The purpose of this review is to provide updated, comprehensive and categorized information on the ethnobotany, phytochemistry and pharmacological research of Litsea species in order to explore their therapeutic potential and evaluate future research opportunities.All the available information on Litsea species was actualised by systematically searching the scientific literatures including Chinese, Korean, Japanese, Indian, and South American herbal classics, library catalogs and scientific databases (PubMed, SciFinder, Web of Science, Google Scholar, VIP and Wanfang). The Plant List, International Plant Name index and Scientific Database of China Plant Species were used to validate scientific names.407 secondary metabolites have been reported from Litsea species. Litsea Species are sources of secondary metabolites with interesting chemical structures (alkaloids, lactones, sesquiterpenes, flavonoids, lignans, and essential oils) and significant bioactivities. Crude extracts, fractions and phytochemical constituents isolated from Litsea show a wide spectrum of in vitro and in vivo pharmacological activities including anticancer, anti-inflammatory, antimicrobial, antioxidant, antidiabetic, anti-HIV, insecticidal, etc.From data collected in this review, the genus Litsea comprises a wide range of therapeutically promising and valuable plants, and has attracted much attention owing to its multiple functions. Many traditional uses of Litsea species have now been validated by modern pharmacology research. Deep and systematic phytochemical investigation of the genus Litsea and the pharmacological properties, especially its mechanism of action and toxicology, to illustrate its ethnomedicinal use, explore the therapeutic potential and support further health-care product development will undoubtedly be the focus of further research. Therefore, detailed and extensive studies and clinical evaluation of Litsea species should be carried out in future for the safety approval of therapeutic applications.

Rectal perforation is an unusual complication of therapeutic colonoscopy. The present study reports the case of a patient with a rare manifestation of pneumothorax, pneumomediastinum, pneumoperitoneum and extensive subcutaneous emphysema that resulted from an endoscopic mucosal resection following a colonoscopy of the rectum. Only 3 cases of colonic perforation and 1 case of rectal perforation have been described previously, of which the clinical diagnoses and treatments were varied, and no results of follow-up studies were reported. In the present study, dyspnea and neck swelling were acute signs of extraluminal air that resulted from rectal perforation. Computed axial tomography was an effective diagnosis method, and is recommended for the early recognition of colorectal perforation. Appropriate management and a close follow-up are crucial for optimal results.

As activin/nodal signaling plays a key role in definitive endoderm (DE) differentiation, we have explored activin A-induced differentiation of DE from human parthenogenetic embryonic stem cells (hPESCs). Administration of 5 ng activin A/ml had no effect on the expression of markers of DE differentiation. However, higher concentrations of activin A (50 and 100 ng/ml) upregulated Sox17 and Cxcr4, as well upregulating the mesendodermal precursor marker, Brachyury. These findings demonstrate that low dose activin A can maintain the undifferentiated potency of hPESCs, whereas higher doses induce DE differentiation; 50 ng/ml is the optimal concentration for inducing DE from hPESCs.

Objectives: This study was designed to obtain the knowledge about TEG indexes distribution in Chinese aged people, as well as to test the hypothesis that previous TEG indexes are associated with the subsequent thromboembolic and bleeding events in the aged population. Methods: We conducted a two-year follow-up study in Chinese PLA General Hospital, Beijing, China. 403 aged people were enrolled in our study. They received TEG measurements at least once when they entered this study. We collected their demographical characteristics, clinical examination information and their outcome during their observational period. Structural equation modeling (SEM) was used to analyze the relationship between the four indexes from TEG and the outcome via a pathway of indicator. Results: We found that in the “model of bleeding” (adjusted by confounding of Anticoagulants), the model fit indices with chi-square/df = 9.555/7, CFI was 0.997, TLI was 0.994 and standardized root mean square residual (SRMR) was 0.034; while in the “model of thromboembolic events” (adjusted by confounding of Anticoagulants), the model fit indices with chi-square/df = 6.070/7, CFI was1.000, TLI was 1.002 and standardized root mean square residual (SRMR) was 0.000. The “model of thromboembolic events” showed that the four indexes (R, K, MA and ANGLE) were all significantly associated with thromboembolic events, while this significance was not found in the “model of bleeding”. Conclusions: Previous TEG indexes are significantly associated with the subsequent thromboembolic events in the aged population. Future study can test this association and provide more information for the clinical use.

In this paper, total dose responses and reliability issues of MOSFETs fabricated by 65 nm CMOS technology were examined. "Radiation-induced narrow channel effect" is observed in a narrow channel device. Similar to total dose responses of NMOSFETs, narrow channel NMOSFEs have larger hot-carrier-induced degradation than wide channel devices. Step Time-Dependent Dielectric Breakdown (TDDB) stresses are applied, and narrow channel devices have higher breakdown voltage than wide channel devices, which agree with "weakest link" theory of TDDB. Experimental results show that linear current, transconductance, saturated drain current and subthreshold swing are superposed degenerated by total dose irradiation and reliability issues, which may result in different lifetime from that considering total dose irradiation reliability issues separately.

In this paper, a series of hot carriers tests of irradiated 130 nm partially depleted silicon-on-insulator NMOSFETs is carried out in order to explore the HCI influence on the ionizing radiation damage. Some devices are irradiated by up to 3000 Gy before testing the hot carriers, while other devices experience hot carriers test only. All the devices we used in the experiments are fabricated by using a 130 nm partially depleted (PD) SOI technology. The devices each have a 6nm-thick gate oxide, 100 nm-thick silicon film, and 145 nm-thick buried oxide, with using shallow trench isolation (STI) for isolation scheme. The irradiation experiments are carried by 60Co- ray at the Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, with a dose rate of 0.8~Gy(Si)/s. During irradiation all the samples are biased at 3.3V, i.e., VGS=3.3V and other pins are grounded, and when the devices are irradiated respectively by total doses of 500, 1000, 2000 and 3000Gy(Si), we test the characteristic curves again. Then 168-hour room temperature anneal experiments are carried out for the irradiated devices, using the same biases under irradiation. The HCI stress condition is chosen by searching for the maximum substrate current. The cumulative stress time is 5000s, and the time intervals are 10, 100, 500, 1000 and 5000s respectively. After each stress interval, the device parameters are measured until stress time termination appears. Through the comparison of characteristic between pre-irradiated and unirradiated devices, we find that the total dose damage results in the enhanced effect of hot carriers: the substrate current value which characterizes the hot carrier effect (for SOI device are the body to the ground current) increases with the increase of total dose, as the pre-irradiated and unirradiated device do under the same conditions of hot carrier stress, the degradations of key electrical parameters are more obvious for the pre-irradiated one. In order to analyze the physical mechanism of the experimental phenomena, the wide channel device is tested too, we also analyze the phenomenon of the decrease of the substrate current of the wide channel device. From the contrasts of pre-irradiated and unirradiated devices, and narrow and wide channel device test results, we can obtain the following conclusions: SOI devices (especially the narrow channel device) with additional ionization irradiation field induced by ionizing radiation enhance the rate of injecting electrons into the silicon dioxide, and produce oxide trap charge and interface states, which leads to the fact that the channel carrier scattering becomes stronger, transfer characteristic curve of the device, output characteristic curve, transconductance curves and the related parameters of VT, GMmax, IDSAT degradation degree increase. So, when designing 130nm PD SOI NMOSFETs which are applied to the space environment, one should make a compromise between radiation resistance and HCI reliability.

Enhancing low dose rate sensitivity (ELDRS) in bipolar device is a major problem of liner circuit radiation hardness prediction for space application. ELDRS is usually attributed to space-charge effect. A key element is the difference in transport rate between holes and protons in SiO2. Interface-trap formation at high dose rate is reduced due to positive charge buildup in the Si/SiO2 interfacial region (due to the trapping of holes and/or protons) which reduces the flow rates of subsequent holes and protons (relative to the low-dose-rate case) from the bulk of the oxide to the Si/SiO2 interface. Generally speaking, the dose rate of metal oxide semiconductor (MOS) device is time dependent when annealing of radiation-induced charge is taken into account. The degradation of MOS device induced by the low dose rate irradiation is the same as that by high dose rate when annealing of radiation-induced charge is taken into account. However, radiation response of new generation MOS device is dominated by charge buildup in shallow trench isolation (STI) rather than gate oxide as older generation device. Unlike gate oxides, which are routinely grown by thermal oxidation, field oxides are produced using a wide variety of deposition techniques. As a result, they are typically thick (100 nm), soft to ionizing radiation, and electric field is far less than that of gate oxide, which is similar to the passivation layer of bipolar device and may lead to ELDRS. Therefore, dose-rate sensitivities of n-type metal oxide semiconductor field effect transistor (NMOSFET) and static random access memory (SRAM) manufactured by 0.18 m complementary metal oxide semiconductor (CMOS) process are explored experimentally and theoretically in this paper. Radiation-induced leakages in NMOSFET and SRAM are examined each as a function of dose rate. Under the worst-case bias, the degradation of NMOSFET is more severe under the low dose rate irradiation than under the high dose rate irradiation and anneal. Moreover, radiation-induced standby current rising in SRAM is more severe under the low dose rate irradiation than under the high dose rate irradiation even when anneal is not considered. The above experimental results reveal that the dose-rate sensitivity of deep sub-micron CMOS process is not related to time-dependent effects of CMOS devices. Mathematical description of the combination between enhanced low dose-rate sensitivity and timedependent effects as applied to radiation-induced leakage in NMOSFET is developed. It has been numerically found that non time-dependent effect of deep sub-micron CMOS device arises due to the competition between enhanced low dose-rate sensitivity in bottom of STI and time-dependent effect at the top of STI. The high dose rate irradiation is overly conservative for devices used in a low dose rate environment. The test method provides an extended room temperature anneal test to allow leakage-related parameters that exceed postirradiation specifications to return to a specified range.

With the development of semiconductor technology, the small size silicon-on-insulator metal-oxide-semiconductor field-effect transistor devices start to be applied to the aerospace field, which makes the device in use face dual challenges of the deep space radiation environment and conventional reliability. The small size device reliability test under ionizing radiation environment is conducible to the assessing of the comprehensive reliability of the device. With reference to the national standard GB2689.1-81 constant stress life test and accelerated life test method for the general electric stress, the conventional reliability of the sub-micron type partially-depleted silicon-on-insulator n-channel metal-oxide-semiconductor is studied under the ionizing radiation environment. The experiment is divided into three groups marked by A, B and C. For all the experimental devices, the gate oxide t(ox) = 12.5 nm, channel length L = 0.8 mu m and width W = 8 mu m, and nominal operating voltage V = 3.5 V. We carry out the electrical stress test on A group after irradiation with gamma-ray dose up to 1 x 10(4) Gy (Si) under the bias condition. Before group B is tested, it has been irradiated by the same dose gamma-ray and annealed for one week. Group C is not irradiated by gamma-ray before the electric stress test. After irradiation we measure the DC characteristics of the devices: the drain current versus gate voltage (I-DS-V-GS) and the drain current versus drain voltage (I-DS-V-DS). The hot carrier injection (HCI) experiment is periodically interrupted to measure the DC characteristics of the device. The sensitive parameters of HCI and irradiation are V-T, GM and IDlin, and after HCI stress, all parameters are degenerated. Through the contrast test, we qualitatively analyze the influences of the oxide trap charge and interface state on the sensitive parameters. We obtain the curve of the oxide trap charge and interface state versus time, and the influences of the different stages on device parameters. The results show that the combination of the total dose radiation environment and electrical stress causes the sensitive parameters of the device to rapidly degrade, this combination of these two factors gives rise to bigger effect than a single influence factor.

In the present paper, function test of different test pattern was used to investigate function failure of static random access memory (SRAM) induced by the total dose effect. By comparing the function test results of different test pattern and single error bit, it is shown that the failure mode of the device is data retention fault, and different storage cell had diverse data retention time, the fault module of device is the storage cell. We discussed the reason for these phenomena in detail using simple circuit model of storage cell, and also analyzed the influence of these phenomena on test method to evaluate the total dose radiation damage of SRAM.