Combining pathological risk factors and T, N staging to optimize the assessment for risk stratification and prognostication in low-risk stage III colon cancer.

BACKGROUND: This study aimed to investigate the combined pathological risk factors (PRFs) to stratify low-risk (pT1-3N1) stage III colon cancer (CC), providing a basis for individualized treatment in the future. PATIENTS AND METHODS: PRFs for low-risk stage III CC were identified using COX model. Low-risk stage III CC was risk-grouped combining with PRFs, and survival analysis were performed using Kaplan-Meier. The Surveillance, Epidemiology, and End Results (SEER) databases was used for external validation. RESULTS: Nine hundred sixty-two stage III CC patients were included with 634 (65.9%) as low risk and 328 (34.1%) as high risk. Poor differentiation (OS: P = 0.048; DFS: P = 0.011), perineural invasion (OS: P = 0.003; DFS: P < 0.001) and tumor deposits (OS: P = 0.012; DFS: P = 0.003) were identified as PRFs. The prognosis of low-risk CC combined with 2 PRFs (OS: HR = 3.871, 95%CI, 2.004-7.479, P < 0.001; DFS: HR = 3.479, 95%CI, 2.158-5.610, P < 0.001) or 3 PRFs (OS: HR = 5.915, 95%CI, 1.953-17.420, P = 0.002; DFS: HR = 5.915, 95%CI, 2.623-13.335, P < 0.001) was similar to that of high-risk CC (OS: HR = 3.927, 95%CI, 2.317-6.656, P < 0.001; DFS: HR = 4.132, 95%CI, 2.858-5.974, P < 0.001). In the SEER database, 18,547 CC patients were enrolled with 10,023 (54.0%) as low risk and 8524 (46.0%) as high risk. Low-risk CC combined with 2 PRFs (OS: HR = 1.857, 95%CI, 1.613-2.139, P < 0.001) was similar to that of high-risk CC without PRFs (HR = 1.876, 95%CI, 1.731-2.033, P < 0.001). CONCLUSION: Combined PRFs improved the risk stratification of low-risk stage III CC, which could reduce the incidence of undertreatment and guide adjuvant chemotherapy.

An n-Dimensional Chaotic Map with Application in Reversible Data Hiding for Medical Images.

The drawbacks of a one-dimensional chaotic map are its straightforward structure, abrupt intervals, and ease of signal prediction. Richer performance and a more complicated structure are required for multidimensional chaotic mapping. To address the shortcomings of current chaotic systems, an n-dimensional cosine-transform-based chaotic system (nD-CTBCS) with a chaotic coupling model is suggested in this study. To create chaotic maps of any desired dimension, nD-CTBCS can take advantage of already-existing 1D chaotic maps as seed chaotic maps. Three two-dimensional chaotic maps are provided as examples to illustrate the impact. The findings of the evaluation and experiments demonstrate that the newly created chaotic maps function better, have broader chaotic intervals, and display hyperchaotic behavior. To further demonstrate the practicability of nD-CTBCS, a reversible data hiding scheme is proposed for the secure communication of medical images. The experimental results show that the proposed method has higher security than the existing methods.

Stem water cryogenic extraction biases estimation in deuterium isotope composition of plant source water.

The hydrogen isotope ratio of water cryogenically extracted from plant stem samples (δ2Hstem_CVD) is routinely used to aid isotope applications that span hydrological, ecological, and paleoclimatological research. However, an increasing number of studies have shown that a key assumption of these applications-that δ2Hstem_CVD is equal to the δ2H of plant source water (δ2Hsource)-is not necessarily met in plants from various habitats. To examine this assumption, we purposedly designed an experimental system to allow independent measurements of δ2Hstem_CVD, δ2Hsource, and δ2H of water transported in xylem conduits (δ2Hxylem) under controlled conditions. Our measurements performed on nine woody plant species from diverse habitats revealed a consistent and significant depletion in δ2Hstem_CVD compared with both δ2Hsource and δ2Hxylem Meanwhile, no significant discrepancy was observed between δ2Hsource and δ2Hxylem in any of the plants investigated. These results cast significant doubt on the long-standing view that deuterium fractionation occurs during root water uptake and, alternatively, suggest that measurement bias inherent in the cryogenic extraction method is the root cause of δ2Hstem_CVD depletion. We used a rehydration experiment to show that the stem water cryogenic extraction error could originate from a dynamic exchange between organically bound deuterium and liquid water during water extraction. In light of our finding, we suggest caution when partitioning plant water sources and reconstructing past climates using hydrogen isotopes, and carefully propose that the paradigm-shifting phenomenon of ecohydrological separation ("two water worlds") is underpinned by an extraction artifact.

Responses of maize (Zea mays L.) seedlings growth and physiological traits triggered by polyvinyl chloride microplastics is dominated by soil available nitrogen.

As a burgeoning pollutant, microplastics (MPs) has elicited global concern. However, ecological effects and mechanisms of MPs on plant-soil system are still poorly understood. In the present study, the impacts of polyvinyl chloride microplastics (PVC-MPs) on maize (Zea mays L.) seedlings growth and physiological traits and soil properties were discussed through a 30-day pot experiment. Results showed that PVC-MPs had greater toxicity effect on seedlings shoot biomass than root biomass. To defense the impact of PVC-MPs, the superoxide dismutase and catalase activities in seedlings leaf were stimulated. Moreover, the adhesion of MPs on soil particles increased, and soil microorganism, enzymes, and nutrients were altered significantly with increasing content of PVC-MPs. Notably, soil nitrate nitrogen decreased significantly with increasing content of PVC-MPs, whereas soil ammonium nitrogen was promoted under lower contents (0.1% and 1%) of PVC-MPs. Redundancy analysis indicated that soil nitrate nitrogen and ammonium nitrogen can explain 87.4% and 7.7% of variation in maize seedlings growth and physiological traits, respectively. These results display that maize seedlings shoot is more susceptible to the impact of PVC-MPs and soil available nitrogen is the primary limiting factor on maize seedlings growth and physiological traits triggered by PVC-MPs. Impacts of PVC-MPs on maize seedlings growth and physiological traits by nitrogen depletion lead to the possible yield and economic loess and potential risks due to the over use of nitrogen fertilizers.

Risk factors for metachronous peritoneal carcinomatosis after radical resection for patients with nonmetastatic pT3-4 colon cancer.

BACKGROUND: Patients with nonmetastatic pT3-4 colon cancers are prone to develop metachronous peritoneal carcinomatosis (mPC). Risk factors for mPC and the influence of mutant kirsten rat sarcoma viral oncogene (KRAS)/neuroblastoma rat sarcoma (NRAS)/v-raf murine sarcoma viral oncogene homolog B1 (BRAF) and DNA mismatch repair (MMR) status on mPC remain to be described in these patients. METHOD: All enrolled patients were identified from the prospectively collected colorectal cancer database of a tertiary referral hospital between 2013 and 2018. Multivariate analysis was used to identify risk factors associated with mPC. RESULTS: Of the 1689 patients with nonmetastatic pT3-4 colon carcinoma, 8.4% (142/1689) progressed to mPC. Endoscopic obstruction (HR = 3.044, p < 0.001), elevated CA125 (HR = 1.795, p = 0.009), pT (T4a vs. T3, HR = 2.745, p < 0.001; T4b vs. T3, HR = 3.167, p = 0.001), pN (N1 vs. N0, HR = 2.592, p < 0.001; N2 vs. N0, HR = 4.049, p < 0.001), less than 12 lymph nodes harvested (HR = 2.588, p < 0.001), mucinous or signet ring cell carcinoma (HR = 1.648, p = 0.038), perineural invasion (HR = 1.984, p < 0.001), and adjuvant chemotherapy (HR = 1.522, p = 0.039) were strongly related to mPC but that mutant KRAS/NRAS/BRAF and MMR status was not associated with mPC. CONCLUSION: This study identified the high-risk factors for mPC in patients with nonmetastatic pT3-4 colon carcinoma, and these factors should be considered in selective preventive therapy and close follow-up for patients subsequently deemed to have high risk for mPC.

Clinicopathological and molecular characteristics of early-onset vs late-onset colorectal cancer according to tumor location.

BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC) is rapidly increasing worldwide in decade when screening of colorectal cancer (CRC) is more prevalent. The clinicopathological and molecular characteristics of EOCRC have not yet been clarified. This study aims to evaluate clinicopathological and molecular features among EOCRC and late-onset colorectal cancer (LOCRC) patients according to different tumor locations. METHODS: We identified CRC patients from a prospectively maintained CRC database between January 2015 and December 2018. The clinicopathological and molecular characteristics including dMMR, mutation of PIK3CA, BRAF and KRAS were compared between EOCRC and LOCRC. The relationships according to different tumor locations were assessed. RESULTS: Totally 4468 patients were analyzed in this study. Compared to LOCRC patients, EOCRC patients were more likely to have status of dMMR (OR, 2.52; P < 0.001), regardless of tumor location. EOCRC patients were more likely to be detected with mutation of PIK3CA (OR, 1.24; P = 0.041), which only tended to exist in the left-side colon (OR, 1.51; P = 0.06), but not in the right-side colon or rectum. No significant difference was found for BRAF or KRAS mutation, but mutation of KRAS was more frequently found in left-side colon (OR, 1.34; P = 0.04) among EOCRC patients. CONCLUSION: Status of dMMR, mutation of PIK3CA, BRAF and KRAS was different between EOCRC and LOCRC patients according to different tumor locations, which implied that EOCRC might be a unique subgroup of CRC patients. Further investigations of molecular and genetic differences should be performed to help define new diagnosing and therapeutical strategies for EOCRC patients.

Does ileoanal pouch surgery increase the risk of desmoid in patients with familial adenomatous polyposis?

PURPOSE: Patients with familial adenomatous polyposis (FAP) may undergo either ileorectal anastomosis (IRA) or ileal pouch anal anastomosis (IPAA) depending on the degree of rectal involvement. Desmoid tumors (DTs) may arise postoperatively. Whether IPAA is associated with a higher risk of DTs as compared with IRA remains controversial. The purpose of this study was to determine whether IPAA increased the risk of DTs by analyzing the published data that compared IRA and IPAA as the primary treatment for FAP. METHODS: A metaanalysis was performed to analyze the published data between 1989 and 2019. IRA and IPAA were compared with respect to the incidence of DTs. RESULTS: Eight retrospective studies with a total of 1072 patients were identified: 491 underwent IPAA and 581 IRA. There was no significant difference in the incidence of DTs between IPAA and IRA (11.81% vs. 9.47%, OR 0.95, P = 0.85). Meanwhile, the overall complication (42.97% vs. 36.76%, OR 1.32, P = 0.11), incidence of cancer (4.88% vs. 8.37%, OR 0.28, P = 0.26), and overall mortality (0.33% vs. 5.20%, OR 0.49, P = 0.53) were comparable too. CONCLUSION: Ileoanal pouch surgery is associated with similar risk of desmoid in patients with FAP after surgery.

A Time-efficient Multi-Protocol Probe Scheme for Fine-grain IoT Device Identification.

Internet of Things (IoT) devices connected to the Internet are exploding, which poses a significant threat for their management and security protection. IoT device identification is a prerequisite for discovering, monitoring, and protecting these devices. Although we can identify the device type easily through grabbing protocol banner information, both brand and model of different types of device are various and diverse. We should therefore utilize multi-protocol probes to improve the fineness of device identification and obtain the corresponding brand and model. However, it is still a challenge to balance between the multi-protocol probe overhead and the identification fineness. To solve this problem, we proposed a time-efficient multi-protocol probe scheme for fine-grain devices identification. We first adopted the concept of reinforcement learning to model the banner-based device identification process into a Markov decision process (MDP). Through the value iteration algorithm, an optimal multi-protocol probe sequence is generated for a type-known IoT device, and then the optimal multi-protocol probes sequence segment is extracted based on the gain threshold of identification accuracy. We took 132,835 webcams as the sample data to experiment. The experimental results showed that our optimal multi-protocol probes sequence segment could reduce the identification time of webcams' brand and model by 50.76% and achieve the identification accuracy of 90.5% and 92.3% respectively. In addition, we demonstrated that our time-efficient optimal multi-protocol probe scheme could also significantly improve the identification efficiency of other IoT devices, such as routers and printers.

Location-Aware Wi-Fi Authentication Scheme Using Smart Contract.

Advanced wireless technology in Internet of Things (IoT) devices is increasing and facing various security threats. The authentication of IoT devices is the first line of defense for the wireless network. Especially in a Wi-Fi network, the existing authentication methods mainly use a password or digital certificate, these methods are inconvenient to manage due to certificate issuance or prone to be attacked because passwords are easily cracked. In this paper, we propose a location-aware authentication scheme using smart contracts to ensure that IoT devices can securely perform Wi-Fi network authentication. The scheme adopts the concept of secondary authentication and consists of two phases: the registration phase, which is mainly designed to complete the generation of the public and private keys, and to link the device information with its related device information; the authentication phase, which is mainly designed to determine whether the requesting device is within a legal location range. We use the smart contract to ensure the credibility and irreparability of the authentication process. Analysis of the attack model and the attacks at different stages proves that this certification scheme is assured, and the simulation results show that the overhead introduced by this scheme is acceptable, this scheme can provide greater security for the Wi-Fi authentication of IoT devices.

Subclinical myocardial dysfunction in coronary slow flow phenomenon: Identification by speckle tracking echocardiography.

OBJECTIVE: This study aimed to determine whether STE could help detect subclinical myocardial dysfunction in patients with CSFP. METHODS: Sixty patients with CSFP confirmed by CAG and 51 controls with normal coronary flow were prospectively enrolled. Coronary angiographic data and conventional and speckle tracking echocardiographic parameters of the LV and RV were obtained for every subject. RESULTS: Compared with controls, CSFP patients presented with higher BMI and TG levels, but lower HDL-C levels. Conventional echocardiographic parameters of biventricular systolic and diastolic function did not differ between the two groups (all P > 0.05). The GLS of the LV and RV was significantly impaired in CSFP patients compared with that in controls (-19.03% vs -21.42%, P < 0.001 and -19.72% vs -22.96%, P = 0.001, respectively). The myocardial impairment pattern of CSFP patients was homogenous in the RV and heterogeneous in the LV, where only endo- and mid-myocardial layers were affected. LV-GLS and RV-GLS were found to be well correlated with mTFC and HDL-C in CSFP groups (r = 0.463 vs r = 0.439; r = -0.569 vs r = -0.552, all P < 0.05). ROC curve analysis demonstrated that LV-GLS-endo had the highest AUC (0.867, P < 0.001) for predicting subclinical myocardial impairment in CSFP patients. CONCLUSIONS: Subclinical myocardial systolic dysfunction occurs in both ventricles, and GLS could be an effective method to detect early-stage myocardial impairment in patients with CSFP.

Assessment of subclinical left ventricular changes in essential hypertensive patients with hyperuricemia: A three-dimensional speckle-tracking echocardiography study.

OBJECTIVE: To evaluate the effect of hyperuricemia (HU) on subclinical changes of left ventricle (LV) function and structure in patients with hypertension (HT) using three-dimensional speckle-tracking echocardiography (3DSTE) and to explore the relationships between serum uric acid (SUA) levels and three-dimensional speckle tracking echocardiography (3DSTE) parameters in hypertensive and nonhypertensive patients with HU. METHODS: Four age- and sex-matched groups were studied: I: healthy controls, HT- HU- (n = 40); II: HT- HU+ (n = 40); III: HT+ HU- (n = 40); IV: HT+ HU+ (n = 44). Conventional echocardiography and 3DSTE were recorded. Relative wall thickness (RWT) and left ventricular mass index assessed by M-mode echocardiography (LVMi-M) were calculated. 3DSTE parameters including LV volumes and ejection fraction (EF), LVMi-3D, global longitudinal strain (GLS), and global circumferential strain (GCS) were compared. The relationships between SUA levels and 3DSTE parameters were investigated. RESULTS: Despite LV diameters, LV volumes and EF were similar among groups (all p > 0.05), GLS decreased and LVMi-3D increased from controls (group I) to patients with HU or HT alone (group II or III), and patients with both HU and HT (group IV) (all p < 0.05). SUA levels were significantly correlated with the absolute value of GLS (r = -0.461, p < 0.05) and LVMi-3D (r = 0.504, p < 0.05) in hypertensive and nonhypertensive patients with HU. CONCLUSIONS: HU may exacerbate LV systolic dysfunction and remodeling in hypertensive patients, which can be detected by 3DSTE. Early uric acid lowing treatment may be beneficial for hypertensive patients with HU.

Wheat (Triticum aestivum L.) seedlings performance mainly affected by soil nitrate nitrogen under the stress of polyvinyl chloride microplastics.

Microplastics are exotic pollutants and are increasingly detected in soil, but it remains poorly understood how microplastics impact soil and plant systematically. The present study was conducted to evaluate the effects of polyvinyl chloride microplastics (PVC-MPs) on wheat seedlings performance and soil properties. Under the stress of PVC-MPs, no new substance and functional groups were generated in soil by X-ray diffraction and the fourier transform infrared spectroscopy analyses, whereas the diffraction and characteristic peaks and of soil was affected by PVC-MPs. Wheat seedlings shoot biomass and soil nitrate nitrogen were significantly inhibited by PVC-MPs. Chlorophylls were not significant affected by PVC-MPs. Superoxide dismutase, catalase, and peroxidase activities in wheat seedlings increased, while malondialdehyde and proline contents decreased significantly. Redundancy analysis displayed that wheat seedlings traits can be largely explained by soil nitrate nitrogen. Our results indicate that PVC-MPs have more significant influence on soil structure than on soil substance composition. Moreover, even though antioxidant enzyme activities were improved to respond the stress of PVC-MPs, wheat seedlings are not severely impacted by PVC-MPs. Besides, soil nitrate nitrogen is the main factor on wheat seedlings performance and wheat seedlings are prone to ensure the root growth under the stress of PVC-MPs.

The safety and effectiveness of prophylactic hyperthermic intraperitoneal chemotherapy in patients with pathological T3-4 locally advanced colon cancer.

INTRODUCTION: The safety and effectiveness of prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) in pathological T3-4 locally advanced (pT3N + M0 and pT4NxM0) colon cancer (CC) patients with radical resection need further study. METHODS: Clinical and pathological information of pT3-4 locally advanced CC patients who received radical surgery in our hospital from January 2018 to December 2020 were analyzed. The prognosis of patients was estimated using Cox proportional hazards regression analysis and Kaplan-Meier method. RESULTS: Among 927 patients, 10.4% (96/927) received prophylactic HIPEC based on 5-FU, 4.6% (43/927) received prophylactic HIPEC based on lobaplatin, 85.0% (788/927) received conventional therapy. The incidence of metachronous peritoneal carcinomatosis (mPC) was 9.4%. Complications occurred in 32 patients (4.1%) in the conventional therapy group, 6 patients (6.3%) in the prophylactic HIPEC group based on 5-FU and 3 patients (7.0%) in the prophylactic HIPEC group based on lobaplatin within 30 days after surgery (5-FU vs. conventional therapy group, p = 0.464; Lobaplatin vs. conventional therapy group, p = 0.591). Multivariate Cox regression analysis revealed that prophylactic HIPEC based on either 5-FU or lobaplatin regimen could not effectively improve mPC-free survival (5-FU: p = 0.020, HR = 1.927, 95% CI, 1.111-3.343; Lobaplatin: p = 0.167, HR = 0.247, 95% CI, 0.034-1.796), overall survival (5-FU: p = 0.361, HR = 1.360, 95% CI, 0.703-2.634; Lobaplatin: p = 0.780, HR = 0.816, 95% CI, 0.195-3.416) and disease-free survival (5-FU: p = 0.525, HR = 1.149, 95% CI, 0.749-1.760; Lobaplatin: p = 0.117, HR = 0.488, 95% CI, 0.199-1.198). CONCLUSION: Early prophylactic HIPEC based on 5-FU or lobaplatin subsequent to radical resection for patients with pT3-4 locally advanced CC is safe, but not effective in reducing the risk for mPC.

Fatty Acid Oxidation Promotes Apoptotic Resistance and Proinflammatory Phenotype of CD4+ Tissue-resident Memory T cells in Crohn's Disease.

BACKGROUND & AIMS: As the most abundant memory T cells and major source of tumor necrosis factor α in the intestinal mucosa of Crohn's disease (CD) patients, CD4+ tissue-resident memory T (TRM) cells play a critical role in CD pathogenesis. We investigated the role of metabolic reprogramming in the regulation of proinflammatory and apoptosis-resistant phenotype for CD4+ TRM cells. METHODS: CD4+ TRM cells were collected from intestinal resection tissues from control and CD patients. Transcriptomic and metabolomic analysis were performed to identify metabolic characteristics of CD4+ TRM cells. Enzyme-linked immunosorbent assay and quantitative polymerase chain reaction experiments were used to assess cytokines level in CD4+ TRM cells; activation-induced cell apoptosis rate was evaluated by flow cytometry. Transwell assay and wound healing assay were performed to detect the effect of CD4+ TRM cells on the migration of normal intestinal epithelial cells. RESULTS: Transcriptomic data combined with unbiased metabolomic analysis revealed an increased fatty acid oxidation (FAO) phenotype existed in CD4+ TRM cells from CD patients. The lipidomic data and stable isotope tracer experiments demonstrated that CD4+ TRM cells up-regulated their lipid lipolysis and fatty acid uptake to fuel FAO in CD patients. Mechanistically, the activated nuclear factor kappa B signaling increased transcription of genes involved in lipid lipolysis, fatty acid uptake, and oxidation in CD4+ TRM cells from CD patients. Targeting FAO of CD4+ TRM cells reversed their apoptosis-resistant and proinflammatory phenotype in CD patients. CONCLUSIONS: CD4+ TRM cells process an accelerated FAO mediated by activated nuclear factor kappa B signaling in CD patients; targeting FAO could reverse their apoptosis-resistant and proinflammatory phenotype. These findings shed a new light on the pathogenic mechanism investigation and novel therapy development in CD patients.

An angled-shape tip-based strategy for highly sensitive proteomic profiling of a low number of cells.

Profiling proteins plays an essential role in understanding the functions and dynamic networks in biological systems. Mass spectrometry-based proteomic analysis commonly requires multistep sample processing, which results in severe sample loss. Although the recently developed microproteomic strategies have substantially reduced sample loss via droplet microfluidic technology, specialized equipment and well-trained personnel are needed, which may limit their wide adoption. Here, we report an angled-shape tip-based strategy for rapid sample preparation and sensitive proteomic profiling of small cell populations (<1000 cells). The angled-shape tip provided a 'reactor' for the entire proteomic sample processing workflow, from cell capture and lysis to protein digestion, eliminating the sample transfer-induced protein loss. The angled-shape tip was surface-treated for anti-protein adsorption which further reduced the sample loss. Using this strategy, 1241 ± 38-4110 ± 37 protein groups and 4010 ± 700-34 879 ± 575 peptides were identified from 10-1000 HeLa cells with high quantification reproducibility in only 4.5 h sample processing time, which was superior to the reported methods and commercial kits, especially for <100 cells. This approach was easily accessible, straightforward to operate, and compatible with flow cytometry-based cell sorting. It showed great potential for in-depth proteomic profiling of rare cells (<1000 cells) in both basic biological research and clinical application.

Changes of left atrial morphology and function evaluated with four-dimensional automated left atrial quantification echocardiography in patients with coronary slow flow phenomenon and preserved left ventricular ejection fraction.

BACKGROUND: Coronary slow flow phenomenon (CSFP) can cause left ventricular diastolic dysfunction (LVDD). In multiple studies, the left atrial (LA) strain has been reported to be an excellent parameter for assessing LVDD. The 4-dimensional automated LA quantification (4D Auto LAQ) dedicated to the LA was recently available. Our study aimed to evaluate subclinical changes in LA morphology and function with 4D Auto LAQ in patients with CSFP and preserved left ventricular ejection fraction (LVEF). METHODS: Forty-eight patients with CSFP confirmed with coronary angiography and 46 age and gender-matched controls with normal coronary flow were enrolled. The thrombolysis in myocardial infarction frame count (TFC) method was used to record coronary blood flow velocities for each major coronary artery. LA volume, LA longitudinal and circumferential strains during each of the three LA phases (reservoir, conduit, and contraction), LA total emptying fraction (LATEF), LA active emptying fraction (LAAEF), and LA passive emptying fraction (LAPEF) were quantified with 4D Auto LAQ analysis. RESULTS: Compared with controls, LA longitudinal reservoir strain (LASr), LA longitudinal strain during the conduit phase (LAScd), LA contraction strain (LASct), LA conduit circumferential strain (LAScd-c), LATEF, LAPEF decreased significantly in individuals with CSFP. Of the 4D- LAQ parameters, only LASr [odds ratio (OR): 0.773, P < 0.001] and LATEF [OR: 0.762, P < 0.001] were associated with CSFP in multivariate analysis. A LASr ≤23.00% can differentiate CSFP from controls [sensitivity, 66.7%; specificity, 93.5%; area under the curve (AUC), 0.823; P < 0.001]. A LASr of ≤19.00% could predict the elevation of LV filling pressure in the CSFP cohort [sensitivity, 76.9%; specificity, 74.3%; area under the curve (AUC), 0.792; P < 0.001]. LASr was the only index to demonstrate significant changes compared to controls in single-vessel CSFP. Compared to the right coronary artery (RCA) and left circumflex (LCX), TFC of the left anterior descending (LAD) artery was the only independent variable of LASr (Standardized Coefficients: -0.386, P = 0.037). CONCLUSIONS: Impairment of LA reservoir function reflected by changes in LASr and LATEF can be seen in patients with CSFP. LASr could predict the elevation of LV filling pressure in CSFP individuals. LASr is more sensitive than LATEF in detecting LA reservoir dysfunction in single-vessel CSFP. CSFP in LAD exerts a more prominent influence on LASr than RCA or LCX.

SPPUSM: An MS/MS spectra merging strategy for improved low-input and single-cell proteome identification.

Single and rare cell analysis provides unique insights into the investigation of biological processes and disease progress by resolving the cellular heterogeneity that is masked by bulk measurements. Although many efforts have been made, the techniques used to measure the proteome in trace amounts of samples or in single cells still lag behind those for DNA and RNA due to the inherent non-amplifiable nature of proteins and the sensitivity limitation of current mass spectrometry. Here, we report an MS/MS spectra merging strategy termed SPPUSM (same precursor-produced unidentified spectra merging) for improved low-input and single-cell proteome data analysis. In this method, all the unidentified MS/MS spectra from multiple test files are first extracted. Then, the corresponding MS/MS spectra produced by the same precursor ion from different files are matched according to their precursor mass and retention time (RT) and are merged into one new spectrum. The newly merged spectra with more fragment ions are next searched against the database to increase the MS/MS spectra identification and proteome coverage. Further improvement can be achieved by increasing the number of test files and spectra to be merged. Up to 18.2% improvement in protein identification was achieved for 1 ng HeLa peptides by SPPUSM. Reliability evaluation by the "entrapment database" strategy using merged spectra from human and E. coli revealed a marginal error rate for the proposed method. For application in single cell proteome (SCP) study, identification enhancement of 28%-61% was achieved for proteins for different SCP data. Furthermore, a lower abundance was found for the SPPUSM-identified peptides, indicating its potential for more sensitive low sample input and SCP studies.