Establishment and validation of a postoperative predictive model for patients with colorectal mucinous adenocarcinoma.

BACKGROUND: The aim of this study was to develop comprehensive and effective nomograms for predicting overall survival (OS) and cancer-specific survival (CSS) rates in patients with colorectal mucinous adenocarcinoma (CRMA). METHODS: A total of 4711 CRMA patients who underwent radical surgery between 2010 and 2018 from the Surveillance, Epidemiology, and End Results (SEER) database were collected and randomized into development (n=3299) and validation (n=1412) cohorts at a ratio of 7:3 for model development and validation. OS and CSS nomograms were developed using the prognostic factors from the development cohort after multivariable Cox regression analysis. The performance of the nomograms was evaluated using Harrell's concordance index (C-index), calibration diagrams, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA). RESULTS: The study included 4711 patients. Multivariate Cox regression analysis demonstrated that age, tumor size, grade, pT stage, pN stage, M stage, carcinoembryonic antigen, perineural invasion, tumor deposits, regional nodes examined, and chemotherapy were correlated with OS and CSS. Marital status was independently related to OS. In the development and validation cohorts, the C-index of OS was 0.766 and 0.744, respectively, and the C-index of CSS was 0.826 and 0.809, respectively. Calibration curves and ROC curves showed predictive accuracy. DCA showed that the nomograms had excellent potency over the 8th edition of the TNM staging system with higher clinical net benefits. Significant differences in OS and CSS were observed among low-, medium-, and high-risk groups. CONCLUSIONS: Nomograms were developed for the first time to predict personalized 1-, 3-, and 5-year OS and CSS in CRMA postoperative patients. External and internal validation confirmed the excellent discrimination and calibration ability of the nomograms. The nomograms can help clinicians design personalized treatment strategies and assist with clinical decisions.

Acupoint application for postherpetic neuralgia with qi stagnation and blood stasis and its effect on related inflammatory factors and 5-HT. / ç©´ä½è´´æ•·æ²»ç–—æ°”æ»žè¡€ç˜€åž‹å¸¦çŠ¶ç–±ç–¹åŽé—ç¥žç»ç—›åŠå¯¹ç›¸å ³ç‚Žæ€§å› å­ã€5-HT的影响.

OBJECTIVES: To observe the clinical efficacy of acupoint application in treating postherpetic neuralgia(PHN) with qi stagnation and blood stasis, and its effects on serum inflammatory factors and 5-hydroxytryptamine (5-HT) in patients. METHODS: A total of 136 PHN patients were randomly divided into an observation group (68 cases, 6 case dropped out) and a control group (68 cases, 5 cases dropped out). In the observation group, the combination of swelling-reducing and pain-relieving patches and acupoint application with herbal powder was used at bilateral Sanyinjiao (SP 6), Shenque (CV 8) and ashi points. Sanyinjiao (SP 6) was applied for 30 min per session, once every 7 days; and Shenque (CV 8) and ashi points were applied for 6-8 h per session, once every 1 day. In the control group, mecobalamin injection was administered at Jiaji (EX-B 2) corresponding to the neural segments governing the painful area, 1 mL per injection, once a day. Each treatment course consisted of 7 days, 4 treatment courses were required in both groups. The visual analog scale (VAS) score for pain, 36-item short form health survey (SF-36) score, traditional Chinese medicine syndrome score, and the serum levels of inflammatory factors (monocyte chemoattractant protein-1 [MCP-1], interleukin-6 [IL-6], tumor necrosis factor-alpha [TNF-α]) and 5-HT were compared in the patients of the two groups before and after treatment, and the clinical efficacy was evaluated. RESULTS: After treatment, the VAS scores, traditional Chinese medicine syndrome scores, serum MCP-1, IL-6, TNF-α, and 5-HT levels were decreased compared with those before treatment in both groups (P<0.05), and the results in the observation group were lower than those in the control group (P<0.05). The SF-36 scores were increased compared with those before treatment in the two groups (P<0.05), and the result in the observation group was higher than that in the control group (P<0.05). The total effective rate of the observation group was 74.2% (46/62), which was higher than 52.4% (33/63, P<0.05) of the control group. CONCLUSIONS: The combination of swelling-reducing and pain-relieving patches and acupoint application with herbal powder has shown better efficacy in treating PHN with qi stagnation and blood stasis, which can significantly alleviate patients symptoms, improve their quality of life, and reduce serum levels of MCP-1, IL-6, TNF-α, and 5-HT.

Novel parallelized quadrupole/linear ion trap/Orbitrap tribrid mass spectrometer improving proteome coverage and peptide identification rates.

Proteome coverage and peptide identification rates have historically advanced in line with improvements to the detection limits and acquisition rate of the mass spectrometer. For a linear ion trap/Orbitrap hybrid, the acquisition rate has been limited primarily by the duration of the ion accumulation and analysis steps. It is shown here that the spectral acquisition rate can be significantly improved through extensive parallelization of the acquisition process using a novel mass spectrometer incorporating quadrupole, Orbitrap, and linear trap analyzers. Further, these improvements to the acquisition rate continue to enhance proteome coverage and general experimental throughput.

TSPAN31 regulates the proliferation, migration, and apoptosis of gastric cancer cells through the METTL1/CCT2 pathway.

Gastric cancer (GC) is one of the most common human malignancies worldwide, but the molecular mechanism of GC has not been fully elucidated. Tetraspanin 31 (TSPAN31) has been rarely studied in human malignant tumors. This study aimed to investigate the effects of TSPAN31 on GC. We analyzed GC tissues through high-throughput sequencing technology and chose TSPAN31 with high expression. The expression of TSPAN31 in GC was analyzed through bioinformatics website and qRT-PCR. The protein level of TSPAN31 in GC tissues was determined by western blot and immunochemistry. The proliferation, migration, and apoptosis of GC cells were detected by the cell counting kit-8, transwell, and apoptosis experiments. METTL1 and CCT2 that may co-express with TSPAN31 were predicted by the GEPIA database, and analyzed the correlation between the expression levels of TSPAN31, METTL1 and CCT2. The results shows TSPAN31 was highly expressed in GC tissues, and high expression of TSPAN31 was found to result in poor prognosis of patients with GC. TSPAN31 could regulate the proliferation, migration and apoptosis of GC cells. The relative expression levels of TSPAN31, METTL1 and CCT2 in GC were positively correlated. Low expression of TSPAN31 could partially reverse the effect of high expression of METTL1 and CCT2 on the tumor progression of GC cells. In conclusion, TSPAN31 was highly expressed in GC tissues and led to poor prognosis of patients with GC. TSPAN31 may regulate the proliferation, migration, and apoptosis of GC cells. This regulatory mechanism may be achieved through co-expression with METTL1 and CCT2.

N7-methylguanosine-related lncRNAs: Predicting the prognosis and diagnosis of colorectal cancer in the cold and hot tumors.

Background: 7-Methylguanosine(m7G) contributes greatly to its pathogenesis and progression in colorectal cancer. We proposed building a prognostic model of m7G-related LncRNAs. Our prognostic model was used to identify differences between hot and cold tumors. Methods: The study included 647 colorectal cancer patients (51 cancer-free patients and 647 cancer patients) from The Cancer Genome Atlas (TCGA). We identified m7G-related prognostic lncRNAs by employing the univariate Cox regression method. Assessments were conducted using univariate Cox regression, multivariate Cox regression, receiver operating characteristics (ROC), nomogram, calibration curves, and Kaplan-Meier analysis. All of these procedures were used with the aim of confirming the validity and stability of the model. Besides these two analyses, we also conducted half-maximal inhibitory concentration (IC50), immune analysis, principal component analysis (PCA), and gene set enrichment analysis (GSEA). The entire set of m7G-related (lncRNAs) with respect to cold and hot tumors has been divided into two clusters for further discussion of immunotherapy. Results: The risk model was constructed with 17 m7G-related lncRNAs. A good correlation was found between the calibration plots and the prognosis prediction in the model. By assessing IC50 in a significant way across risk groups, systemic treatment can be guided. By using clusters, it may be possible to distinguish hot and cold tumors effectively and to aid in specific therapeutic interventions. Cluster 1 was identified as having the highest response to immunotherapy drugs and thus was identified as the hot tumor. Conclusion: This study shows that 17 m7G-related lncRNA can be used in clinical settings to predict prognosis and use them to determine whether a tumor is cold or hot in colorectal cancer and improve the individualization of treatment.

DigestPath: A benchmark dataset with challenge review for the pathological detection and segmentation of digestive-system.

Examination of pathological images is the golden standard for diagnosing and screening many kinds of cancers. Multiple datasets, benchmarks, and challenges have been released in recent years, resulting in significant improvements in computer-aided diagnosis (CAD) of related diseases. However, few existing works focus on the digestive system. We released two well-annotated benchmark datasets and organized challenges for the digestive-system pathological cell detection and tissue segmentation, in conjunction with the International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI). This paper first introduces the two released datasets, i.e., signet ring cell detection and colonoscopy tissue segmentation, with the descriptions of data collection, annotation, and potential uses. We also report the set-up, evaluation metrics, and top-performing methods and results of two challenge tasks for cell detection and tissue segmentation. In particular, the challenge received 234 effective submissions from 32 participating teams, where top-performing teams developed advancing approaches and tools for the CAD of digestive pathology. To the best of our knowledge, these are the first released publicly available datasets with corresponding challenges for the digestive-system pathological detection and segmentation. The related datasets and results provide new opportunities for the research and application of digestive pathology.

Multiplexed four-channel rectilinear ion trap mass spectrometer.

A four-channel multiplexed mass spectrometer with rectilinear ion trap (RIT) mass analyzers was designed, constructed, and characterized. The system consists of four parallel atmospheric pressure ion (API) sources, four RIT mass analyzers, four sets of ion optical elements, and four conversion dynode detectors. The complete instrument is housed in a single vacuum manifold with a common vacuum system. It has a relatively small footprint, and costs and complexity were minimized and controls simplified by sharing the electronics and control modules among different channels. Each channel of the instrument can be operated in either positive or negative ion mode with a choice of ionization methods to improve the information content from an experiment. Also, the instrument is equipped with simultaneous data acquisition capabilities from all four channels, but the use of a common RF electronics system limits the degree to which the analyzer channels can be scanned independently. The instrument was characterized over the mass/charge range of 150 to 1300 Th. Mass misassignments in different ion traps because of machining and assembly tolerances were avoided by the application of supplementary direct current signals to each mass analyzer to correct mass offsets. A multiplexed automatic gain control (AGC) scheme was developed to control the ion population in each of the traps independently. These two features allow tandem mass spectrometry to be performed with an isolation window of 1 Th so trapping identical ions in all four channels. There are two principal modes of operation. In one, the same sample is analyzed in all four channels using different ionization methods to increase the information content of the analysis. In the other mode of operation, different samples are analyzed in all four channels with the same ionization method, so providing higher throughput. These capabilities were demonstrated by examining lipids produced by Escherichia coli and complex mixtures containing drugs of abuse.

Mass selection of ions from beams using waveform isolation in radiofrequency quadrupoles.

A waveform isolation method is described for the mass-selective transmission of ions through quadrupole mass filters, and it is implemented on a new tandem mass analyzer instrument. The method features the application of broad-band waveforms comprising appropriate frequencies to cause mass-selective instability in ions of particular mass-to-charge (m/z) and to transmit all others. The experiment is implemented in a tandem quadrupole system in which the first mass filter is a rectilinear ion trap (RIT) operated in a continuous mass-selective mode to transmit ions of ions of one or more arbitrarily selected m/z value(s). The second analyzer was used to verify the quality of the mass selection achieved using the first analyzer via conventional quadrupole ion trap mass-selective instability scanning. A new subtype of product ion tandem mass spectrometry (MS/MS) scan, termed the summed product ion scan, is demonstrated with a mixture of biological compounds. It is used to characterize product ions arising after simultaneous isolation and collisional activation of multiple precursor species, in this case ions of the same analyte generated in different charge states. The summed product ion scan can be useful for enhancing sensitivity for the analyte of interest or for providing more comprehensive information about an analyte than is available by monitoring a single ionized form of the analyte. The analytical performance of the waveform isolation method is tested using simple drug mixtures, and its potential for increasing overall yields in preparative mass spectrometry is explored briefly. It is shown that efficiencies of ca. 70% of ion transfer to a surface for ion soft landing surface can be achieved. The upper mass range is limited by axial acceleration arising from the stretched geometry, and one solution to this problem is provided.

A new phenolic glycoside from the aerial parts of Dryopteris fragrans.

A new phenolic glycoside, 3,5-dimethyl-6-hydroxy-2-methoxy-4-O-D-glucopyranosyl-oxy-acetophenone (1), was isolated from the aerial parts of Dryopteris fragrans. The structure was elucidated on the basis of spectroscopic methods.

Glow discharge electron impact ionization source for miniature mass spectrometers.

A glow discharge electron impact ionization (GDEI) source was developed for operation using air as the support gas. An alternative to the use of thermoemission from a resistively heated filament electron source for miniature mass spectrometers, the GDEI source is shown to have advantages of long lifetime under high-pressure operation and low power consumption. The GDEI source was characterized using our laboratory's handheld mass spectrometer, the Mini 10. The effects of the discharge voltage and pressure were investigated. Design considerations are illustrated with calculations. Performance is demonstrated in a set of experimental tests. The results show that the low power requirements, mechanical ruggedness, and quality of the data produced using the small glow discharge ion source make it well-suited for use with a portable handheld mass spectrometer.

Novel linear ion trap mass analyzer composed of four planar electrodes.

A novel linear ion trap mass analyzer was developed using just four elongated planar electrodes, mounted in parallel, and employing an RF potential for ion trapping in the radial and axial directions. Mass analysis was achieved using the mass-selective instability scan with ion ejection in the radial direction. The performance of this new device was characterized in comparison with the 6-electrode rectilinear ion trap (RIT) from which it is derived. The 4-electrode trap gives optimum performance in an asymmetric geometry, just like the original optimized 6-electrode RIT. The strong RF fringing fields at the ends of the RF rods account for axial ion trapping without use of extra electrodes or an axial DC voltage. Field calculations and simulations have been carried out to study the trapping potential inside RITs with various configurations. Demonstrated capabilities include analysis of externally injected ions with mass resolution in excess of 1000 and a mass/charge range of 650 Th as well as tandem mass spectrometry capabilities. The geometric simplicity and performance characteristics of the 4-electrode RIT make it particularly attractive in the development of next generation miniaturized mass spectrometers.

Ion trap mass analysis at high pressure: an experimental characterization.

In recent years, it has become increasingly interesting to understand the performance of mass spectrometers at pressures much higher than those employed with conventional operating conditions. This interest has been driven by several influences, including demand for the development of reduced-power miniature mass spectrometers, desire for improved ion transfer into and through mass spectrometers, enhanced-yield preparative mass separations, and mass filtering at the atmospheric pressure interface. In this study, an instrument was configured to allow for the performance characterization of a rectilinear ion trap (RIT) at pressures up to 50 mtorr with air used as the buffer gas. The mass analysis efficiency, mass resolution, isolation efficiency, and collision-induced dissociation (CID) efficiency were evaluated at pressures ranging from 1 to 50 mtorr. The extent of degradation of mass resolution, isolation efficiency and ion stability as functions of pressure were characterized. Also, the optimal resonance ejection conditions were obtained at various pressures. Operations at 50 mtorr demonstrated improved CID efficiency in addition to peak widths of 2 and 5 m/z units (full width at half-maximum, FWHM) for protonated caffeine (m/z 195) and Ultramark (m/z 1521) respectively.

Ion trap mass analysis at high pressure: a theoretical view.

The mass-selective manipulation of ions at elevated pressure, including mass analysis, ion isolation, or excitation, is of great interest for the development of mass spectrometry instrumentation, particularly for systems in which ion traps are employed as mass analyzers or storage devices. While experimental exploration of high-pressure mass analysis is limited by various difficulties, such as ion detection or electrical discharge at high-pressure, theoretical methods have been developed in this work to study ion/neutral collision effects within quadrupole ion traps and to explore their performance at pressures up to 1 Torr. Ion trapping, isolation, excitation, and resonance ejection were investigated over a wide pressure range. The theoretically calculated data were compared with available experimental data for pressures up to 50 mTorr, allowing the prediction of ion trap performance at pressures more than 10 times higher.

Handheld rectilinear ion trap mass spectrometer.

A shoebox-sized, 10-kg, handheld mass spectrometer, Mini 10, based on a rectilinear ion trap mass analyzer has been designed, built, and characterized. This instrument has evolved from a decade-long experimental and simulation program in mass spectrometer miniaturization. The rectilinear ion trap has a simplified geometry and high trapping capacity, and when used with a miniature and ruggedized pumping system, it allows chemical analysis while the instrument is being carried. Compact electronics, including an air core RF drive coil, were developed to control the instrument and to record mass spectra. The instrument runs on battery power, consuming less than 70 W, similar to a laptop computer. Wired and wireless networking capabilities are implemented. The instrument gives unit resolution and a mass range of over m/z 500. Tandem mass spectrometry capabilities are implemented using collision-induced dissociation, and they are used to provide confirmation of chemical structure during in situ analysis. Continuous monitoring of air and solution samples is demonstrated, and a limit of detection of 50 ppb was obtained for toluene vapor in air and for an aqueous naphthalene solution using membrane sample introduction.

Rectilinear ion trap mass spectrometer with atmospheric pressure interface and electrospray ionization source.

A rectilinear ion trap (RIT) mass analyzer was incorporated into a mass spectrometer fitted with an electrospray ionization source and an atmospheric pressure interface. The RIT mass spectrometer, which was assembled in two different configurations, was used for the study of biological compounds, for which performance data are given. A variety of techniques, including the use of a balanced rf, elevated background gas pressure, automatic gain control, and resonance ejection waveforms with dynamically adjusted amplitude, were applied to enhance performance. The capabilities of the instrument were characterized using proteins, peptides, and pharmaceutical drugs. Unit resolution and an accuracy of better than m/z 0.2 was achieved for mass-to-charge (m/z) ratios up to 2000 Th at a scan rate of approximately 3000 amu/(charge.s) while reduced scan rates gave greater resolution and peak widths of less than m/z 0.5 over the same range. The mass discrimination in trapping externally generated ions was characterized over the range m/z 190-2000 and an optimized low mass cutoff value of m/z 120-140 was found to give equal trapping efficiencies over the entire range. The radial detection efficiency was measured as a function of m/z ratio and found to rise from 35% at low m/z values to more than 90% for ions of m/z 1800. The way in which the ion trapping capacity depends on the dc trapping potential was investigated by measuring the mass shift due to space charge effects, and it was shown that low trapping potentials minimize space charge effects by increasing the useful volume of the device. The collision-induced dissociation (CID) capabilities of the RIT instrument were evaluated by measuring isolation efficiency as a function of mass resolution as well as measuring peptide CID efficiencies. Overall CID efficiencies of more than 60% were easily reached, while isolation of an ion with unit resolution at m/z 524 was achieved with high rejection (>95%) of the adjacent ions. The overall analytical capabilities of the ESI-RIT instrument were demonstrated with the analysis of a mixture of pharmaceutical compounds using multiple-stage mass spectrometry.