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Abstract Liver metastasis remains the primary cause of mortality in patients with colon cancer. Identifying specific driver gene mutations that contribute to metastasis may offer viable therapeutic targets. To explore clonal evolution and genetic heterogeneity within the metastasis, we conducted single-cell exome sequencing on 150 single cells isolated from the primary tumor, liver metastasis, and lymphatic metastasis from a stage IV colon cancer patient. The genetic landscape of the tumor samples revealed that both lymphatic and liver metastases originated from the same region of the primary tumor. Notably, the liver metastasis was derived directly from the primary tumor, bypassing the lymph nodes. Comparative analysis of the sequencing data for individual cell pairs within different tumors demonstrated that the genetic heterogeneity of both liver and lymphatic metastases was also greater than that of the primary tumor. This finding indicates that liver and lymphatic metastases arose from clusters of circulating tumor cell (CTC) of a polyclonal origin, rather than from a single cell from the primary tumor. Single-cell transcriptome analysis suggested that higher EMT score and CNV scores were associated with more polyclonal metastasis. Additionally, a mutation in the TRPS1 (Transcriptional repressor GATA binding 1) gene, TRPS1 R544Q, was enriched in the single cells from the liver metastasis. The mutation significantly increased CRC invasion and migration both in vitro and in vivo through the TRPS1R544Q/ZEB1 axis. Further TRPS1 mutations were detected in additional colon cancer cases, correlating with advanced-stage disease and inferior prognosis. These results reveal polyclonal seeding and TRPS1 mutation as potential mechanisms driving the development of liver metastases in colon cancer.

Abstract The correlation between body mass index (BMI) and the development of cough, shortness of breath, and dyspnea is unclear. Therefore, this study aimed to investigate the association between these parameters. Data from individuals who participated in the National Health and Nutrition Examination Survey between 2003 and 2012 were analyzed. Weighted logistic regression analysis and smoothed curve fitting were used to examine the correlation between BMI and respiratory symptoms. In addition, the relationship between BMI, chronic obstructive pulmonary disease (COPD), and bronchial asthma was examined. Stratified analysis was used to discover inflection points and specific groups. Weighted logistic regression and smoothed curve fitting revealed a U-shaped relationship between BMI and respiratory symptoms. The U-shaped relationship in BMI was also observed in patients with bronchial asthma and COPD. Stratified analysis showed that the correlation between BMI and wheezing and dyspnea was influenced by race. In addition, non-Hispanic black individuals had a higher risk of developing cough than individuals of the other three races [OR 1.040 (1.021, 1.060), p

Abstract Background The application of virtual reality (VR) in gastroscopic operation teaching can be safe and effective, but the advantages can be realized only when students accept and use it. This study aims to identify the factors influencing Chinese clinical medical postgraduates on their intention to use the 3D gastroscopic model constructed based on VR technology using Unified Theory of Acceptance and Use of Technology (UTAUT) model. Students’ demographic factors are also taken into consideration. Methods All methods were carried out in accordance with relevant guidelines. Data were collected from clinical medical postgraduates students in China using stratified sampling. A total of 292 questionnaires including valid responses were used in this study. Data were processed using Amos 24.0 and SPSS 26.0 software and the statistical analysis technique was based on structural equation modeling (SEM). Results The results showed that different from the mediator of home location and year of clinical learning, mediator of gender, university kind and graduate degree did not affect the behavioral intention. In addition, performance expectancy, facilitating condition, and social influence directly and indirectly have effect on behavioral intention. Also, the significance between social influence and performance expectancy, social influence and effort expectancy were verified. Conclusions This study manifested that the proposed framework based on the UTAUT had explanatory power to identify the factors influencing the students’ behavioral intention to use the 3D gastroscopic model constructed based on VR technology. Whereas, an important variable of effort expectancy in the frame of the SEM were not certified, thereby indicating that particular attention should be paid to this variable by universities and teachers before applying 3D gastroscopic model constructed based on VR technology in teaching. Added preparatory work is required such as explaining the basic knowledge of the operating steps of VR model and make students adequately understand its accessibility, which can probably improve the intentions of them to use it. The positive effects of social influence on performance expectancy and effort expectancy we proposed was also verified in this study, which provided a direction for future research.

Abstract Objective To systematically evaluate several factors of persistent human papillomavirus (HPV) infection following conization in patients with cervical intraepithelial neoplasia (CIN). Methods PubMed, EMBASE and the Cochrane Library were searched from January 1, 1998 to September 10, 2021. Random-effects models for meta-analyses were used and pooled relative risks with 95% confidence intervals were reported. Literature screening, data extraction, and assessment of the risk of bias in the included studies were conducted independently by two researchers. Data analysis was performed with Stata software, version 12.0. Results A total of 28 studies were included in this study. Meta-analysis revealed that surgical margin and residual disease were positively correlated with persistent HPV infection after conization. Compared with patients infected with other types of HPV, CIN patients with HPV 16 had a higher persistent infection rate (OR = 1.967, 95% CI (1.232–3.140), P

Purpose Although Roussouly classification has been widely used in spinal surgery, it was mainly applied to degenerative scoliosis patients and correlational studies concerning adolescent idiopathic scoliosis (AIS) are still insufficient. This retrospective study explored the clinical application of Roussouly classification in surgeries and prognosis prediction for AIS. Methods This clinical research selected 101 AIS patients who received surgeries between August 2005 and November 2019. Whole spine standing radiographs were obtained for each patient preoperatively, postoperatively, and at the last follow‐up (>24 months). All patients were classified into “theoretical types” and “current types.” Patients were further divided into mismatch or match groups based on the consistency of their current type and theoretical type. The main parameters include: proximal junctional angle (PJA), pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), fixed thoracic kyphosis (TK), global TK, fixed lumbar lordosis (LL), global LL, thoracic tilt, proximal thoracic alignment (PTA), lumbar tilt, spino‐sacral angle (SSA), and spinal tilt (ST). Results A total of 47.5% of AIS patients were subject to a preoperative mismatch of Roussouly classification. There was a significant difference in PI‐LL between the preoperative mismatch and match groups (p = 0.008). There was a significant difference in the rate of PI‐LL deformity between the match and mismatch groups with a preoperative mismatch (p = 0.037). A significant difference in thoracic tilt was observed between the postoperative mismatch and match groups (p = 0.019). The preoperative mismatch group has a higher risk of postoperative PI‐LL malformation than match group (OR = 2.303, 95% CI: 1.026, 5.165). When mismatch occurred postoperatively, there were significant differences between groups in the rate of pelvic deformity (p = 0.002) and PI‐LL deformity (p = 0.025) at the last follow‐up. Compared with the postoperative match group, mismatch group had an increased risk of pelvic deformity (OR = 5.029, 95% CI: 1.618, 15.629) and PJK deformity (OR = 3.017, 95% CI: 1.709, 11.375) at the last follow‐up. Short Form‐36 and Scoliosis Research Society 22 score of the match group was significantly higher than that of the mismatch group at the last follow‐up. Conclusion The Roussouly classification mismatch before or after operation leads to increased risks of PI‐LL deformity and pelvis deformity postoperatively or at the follow‐up, which seriously worsens the clinical symptoms and prognosis of patients. Therefore, recovering to the theoretical type in Roussouly classification may effectively improve patients' prognosis.

This study determined to investigate a strain of Lactobacillus plantarum-Gm4 (LP-GM4) isolated from the traditional sourdough. A response surface experiment was designed according to Box-Behnken central combination principle to optimize the fermentation conditions of LP-Gm4 based on the single factor experiment, and low temperature drying technology was used to prepare sourdough powder. The results showed that the optimal fermentation parameters of LP-GM4 were as follows: fermentation temperature of 31.8 ℃, fermentation time of 13.5 h and LP-Gm4 adding amount of 10 lg(CFU/g) wheat flour. The pH, TTA value and LP-GM4 bacteria count of the sourdough powder were 3.51, 17.8 and 7.2×108 CFU/g, respectively. The sourdough inoculated with LP-Gm4 and active dry yeast were used to prepare the steamed bread, using the single time fermentation progress. The skin structure, internal elasticity, taste and smell of the steamed bread were determined to be superior compared to the yeast steamed bread.

PurposeRecently, totally laparoscopic ileostomy reversal (TLAP) has received increasing attention and exhibited promising short-term outcomes. The aim of this study was to detail the learning process of the TLAP technique.MethodsBased on our initial experience with TLAP from 2018, a total of 65 TLAP cases were enrolled. Demographics and perioperative parameters were assessed using cumulative sum (CUSUM), moving average, and risk-adjusted CUSUM (RA-CUSUM) analyses.ResultsThe overall mean operative time (OT) was 94 min and the median postoperative hospitalization period was 4 days, and there was an estimated 10.77% incidence rate of perioperative complications. Three unique phases of the learning curve were derived from CUSUM analysis, and the mean OT of phase I (1–24 cases) was 108.5 min, that of phase II (25–39 cases) was 92 min, and that of phase III (40–65 cases) was 80 min, respectively. There was no significant difference in perioperative complications between these 3 phases. Similarly, moving average analysis indicated that the operation time was reduced significantly after the 20th case and reached a steady state after the 36th case. Furthermore, complication-based CUSUM and RA-CUSUM analyses indicated an acceptable range of complication rates during the whole learning period.ConclusionOur data demonstrated 3 distinct phases of the learning curve of TLAP. For an experienced surgeon, surgical competence in TLAP can be grasped at around 25 cases with satisfactory short-term outcomes.

Abstract The glycoprotein alpha-1-antichymotrypsin (AACT), a serine protease inhibitor, is mainly synthesized in the liver and then secreted into the blood and is involved in the acute phase response, inflammation, and proteolysis. The dysregulation of AACT and its glycosylation levels are associated with tumor progression and recurrence, and could be used as a biomarker for tumor monitoring. In this review, we summarized the expression level, glycosylation modification, and biological characteristics of AACT during inflammation, neurodegenerative or other elderly diseases, and tumorigenesis, as well as, focused on the biological roles of AACT in cancer. The aberrant expression of AACT in cancer might be due to genetic alterations and/or immune by bioinformatics analysis. Moreover, AACT may serve as a diagnostic or prognostic biomarker or therapeutic target in tumors. Furthermore, we found that the expression of AACT was associated with the overall survival of patients with human cancers. Decreased AACT expression was associated with poor survival in patients with liver cancer, increased AACT expression was associated with shorter survival in patients with pancreatic cancer, and decreased AACT expression was associated with shorter survival in patients with early lung cancer. The review confirmed the key roles of AACT in tumorigenesis, suggesting that the glycoprotein AACT may serve as a biomarker for tumor diagnosis and prognosis, and could be a potential therapeutic target for human diseases.

Abstract Background Saussurea involucrata (SAIN), also known as Snow lotus (SI), is mainly distributed in high-altitude areas such as Tibet and Xinjiang in China. To identify novel targets for the prevention or treatment of lung adenocarcinoma and lung squamous cell carcinoma (LUAD&LUSC), and to facilitate better alternative new drug discovery as well as clinical application services, the therapeutic effects of SAIN on LUAD&LUSC were evaluated by gene differential analysis of clinical samples, compound target molecular docking, and GROMACS molecular dynamics simulation. Results Through data screening, alignment, analysis, and validation it was confirmed that three of the major active ingredients in SAIN, namely quercetin (Q), luteolin (L), and kaempferol (K), mainly act on six protein targets, which mainly regulate signaling pathways in cancer, transcriptional misregulation in cancer, EGFR tyrosine kinase inhibitor resistance, adherens junction, IL-17 signaling pathway, melanoma, and non-small cell lung cancer. In addition, microRNAs in cancer exert preventive or therapeutic effects on LUAD&LUSC. Molecular dynamics (MD) simulations of Q, L, or K in complex with EGFR, MET, MMP1, or MMP3 revealed the presence of Q in a very stable tertiary structure in the human body. Conclusion There are three active compounds of Q, L, and K in SAIN, which play a role in the treatment and prevention of non-small cell lung cancer (NSCLC) by directly or indirectly regulating the expression of genes such as MMP1, MMP3, and EGFR.

Limited knowledge currently exists regarding the dynamics of generational shifts in food consumption among adult residents in China. This study aimed to investigate the generational differences in dietary status among different generations of Chinese adult residents aged 20 years and older. Survey participants from four waves (1991, 2000, 2009, and 2018) of the China Health and Nutrition Survey (CHNS) cohort were included in the study (N = 40,704), providing three-day 24 h dietary data. Participants were categorized into six age groups (20–29, 30–39, 40–49, 50–59, 60–69, and ≥70 years old), each corresponding to specific generations (Gen 10, 20, 30, 40, 50, 60, 70, 80, and 90) based on their age at the time of the survey. This study examined generational differences in the intake of cereals, animal-based foods, vegetables, fruits, dairy, energy, and the contribution of macronutrients to energy using chi-square tests and Kruskal–Wallis tests. All analyses were stratified by gender. Our findings revealed that younger generations exhibited lower daily intake of cereals, vegetables, energy, and contribution of carbohydrates to energy, compared to their older counterparts, regardless of gender. Conversely, regardless of male or female, younger generations showed higher daily consumption of animal-based foods, average fruit and dairy intake, fruit and dairy consumption rates, as well as contributions of protein and fat to energy, compared to older generations. The magnitude of generational differences in food consumption varied by age and gender. In addition, cereal and vegetable intake, energy intake, and contribution of carbohydrates to energy declined with age across all generations, while average dairy intake, fruit and dairy consumption rates, and the contribution of fat to energy tended to increase, regardless of gender. In conclusion, generational differences in food consumption were evident among different generations of Chinese adult residents, characterized by an increase in animal-based food intake and the contribution of fat to energy among generations. Attention should be directed towards addressing the eating behavior of younger generations.

Abstract Mixed human umbilical cord‐derived mesenchymal stem cells (UC‐MSCs) are widely applied in clinical trials to treat various diseases due to their multipotent differentiation potential and immune regulatory activities. However, the lack of a clear understanding of their heterogeneity hampers their application to precisely treat diseases. Moreover, few studies have experimentally authenticated the functions of so‐called UC‐MSC subpopulations classified from scRNA‐seq samples. Here, this work draws a large‐scale single‐cell transcriptomic atlas and identified three clusters (C1, C2, and C3), representing the primed, intermediate, and stem statuses individually. The C1 and C3 clusters feature higher expression of cytokines and stemness markers, respectively. Surprisingly, further experimental assays reveal that the BAMBIhighMFGE8high C1 subgroup has a unique phenotype, distinct transcriptomic profile, and limited adipogenic differentiation potential but compromised immunosuppressive activity in vitro and in vivo in lupus mice. Thus, this work is helpful to clarify the nature of human UC‐MSCs and to choose optimal MSC types to treat specific diseases in the future.

BackgroundThe diagnosis and surgical strategy of lateral lymph node metastases of rectal neuroendocrine tumors are still controversial. At present, the major diagnostic means rely on imaging examinations, but will be affected by the size of lymph nodes leading to false negativity. We provide a new technique to determine lateral lymph node metastases during surgery.Clinical caseA 68-year-old man developed abdominal pain, bloating and fever for a month. Colonoscopy revealed the mass is 2.4 cm x 2.0 cm in size, with a wide stratum, poor mobility, and a rough but intact surface mucosa. Therefore, rectal neuroendocrine tumors (R-NET) were diagnosed. Multiple imaging methods, such as CT, octreotide imaging and endoscopic ultrasonography, have not found lateral lymph node metastases from rectal neuroendocrine tumors. But indocyanine green (ICG)-enhanced near-infrared fluorescence-guided imaging during surgery found left lateral lymph nodes metastases, which was proved by postoperative pathological examination.ConclusionsWe believe that applying ICG-enhanced near-infrared fluorescence-guided imaging in laparoscope can improve the detection of positive LLNs in those R-NET patients who did not reveal LNM on imaging examinations.

Embodied theories of semantic cognition predict that brain regions involved in motion perception are engaged when people comprehend motion concepts expressed in language. Left lateral occipitotemporal cortex (LOTC) is implicated in both motion perception and motion concept processing but prior studies have produced mixed findings on which parts of this region are engaged by motion language. We scanned participants performing semantic judgements about sentences describing motion events and static events. We performed univariate analyses, multivariate pattern analyses (MVPA) and psychophysiological interaction (PPI) analyses to investigate the effect of motion on activity and connectivity in different parts of LOTC. In multivariate analyses that decoded whether a sentence described motion or not, the middle and posterior parts of LOTC showed above-chance level performance, with performance exceeding that of other brain regions. Univariate ROI analyses found the middle part of LOTC was more active for motion events than static ones. Finally, PPI analyses found that when processing motion events, the middle and posterior parts of LOTC (overlapping with motion perception regions), increased their connectivity with cognitive control regions. Taken together, these results indicate that the more posterior parts of LOTC, including motion perception cortex, respond differently to motion vs. static events. These findings are consistent with embodiment accounts of semantic processing, and suggest that understanding verbal descriptions of motion engages areas of the occipitotemporal cortex involved in perceiving motion.

BackgroundThe recognition of new diagnostic and prognostic biological markers for lung cancer, the most severe malignant tumor, is an essential and eager study. In a microenvironment, superoxide dismutase 3 (SOD3) can adjust active oxygen, and it refers to a secreted antioxidant enzyme. It was also found to be cancer-related, and in lung cancer, it was remarkably down-regulated. More and more new cancer research focuses on the function of SOD3. Despite this, there is no good description of SOD3 function in the LC progression.MethodsThrough bioinformatics analysis, we found that SOD3 was a possible novel lung cancer gene in this study. We analyzed data sets from Gene Expression Comprehensive Database (GEO) and the Cancer Genome Atlas (TCGA), and SOD3 expression was studied in lung cancer. This study estimated the SOD3 diagnosis and prognosis through gene expression differential display, gene set enrichment analysis (GSEA), enrichment and genomes (KEGG) analysis, and gene ontology (GO). Then in order to investigate the SOD3 presentation in lung cancer cells, we used Western Blot and also applied Flow cytometry to detect the impact of anti-tumor medicine on tumor cell apoptosis.ResultsWe found that the expression level of SOD3 in lung cancer was low (P = 4.218E-29), while the survival of lung cancer patients with high SOD3 expression was shorter (LUSC p =0.00086, LUAD p=0.00038). According to the result of western blot, the expression of SOD3 in tumor cells was higher than that in normal cells. The ratio of early apoptosis induced by anti-cancer drugs was 10.5% in normal cells, 35.1% in squamous cell carcinoma and 36.9% in adenocarcinoma.The SOD3 high expression was associated with poor survival probability by multivariate analysis (HR: 1.006, 95% CI 1.002–1.011, p=0.006). Moreover, SOD3 high expression group had higher ESTIMATE scores, and larger amount of immune infiltrating cells. SOD3 expression is correlated with PDCD1 and CTLA4 expression.ConclusionsSOD3 gene can be used as a prognostic gene in lung cancer patients, and lung cancer patients with high expression of this gene can reap worse prognostic outcome. It can be used as a new clinical method and prognosticator for lung cancer patients.

In a continuous downhill section of a mountain highway, factors such as road alignment, roadside environment, and other visual characteristics will impact the slope illusion drivers experience and engage in unsafe driving behaviors. To improve the negative consequences of slope illusion and driving safety in continuous downhill sections, the effects of plant spacing, height, roadside distance, and color on driving behavior were all studied by simulating the plant landscape in a virtual environment. A driving simulator and UC-win/road software were used to conduct an indoor driving simulation experiment, and parameters such as speed and lateral position offset were used as the evaluation indices of driving stability to reflect the driver’s speed perception ability with subjective equivalent speeds. The results show that a plant landscape with appropriate plant spacing, height, roadside separation, and color is conducive to improving driving stability. Furthermore, a landscape with a height of 3 m, spacing of 10 m, roadside spacing of 0.75 m, and appropriate color matching can enhance the slope perception ability and speed perception ability of drivers, which is conducive to improving the driving safety of continuous downhill sections.

Diverse classes of anion transporters have been developed, most of which focus on the transmembrane chloride transport due to its significance in living systems. Fluoride transport has, to some extent, been overlooked despite the importance of fluoride channels in bacterial survival. Here, we report the design and synthesis of a cyclic azapeptide (a peptide-based N-amidothiourea, 1), as a transporter for fluoride transportation through a confined cavity that encapsulates fluoride, together with acyclic control compounds, the analogs 2 and 3. Cyclic receptor 1 exhibits more stable β-turn structures than the control compounds 2 and 3 and affords a confined cavity containing multiple inner –NH protons that serve as hydrogen bond donors to bind anions. It is noteworthy that the cyclic receptor 1 shows the capacity to selectively transport fluoride across a lipid bilayer on the basis of the osmotic and fluoride ion-selective electrode (ISE) assays, during which an electrogenic anion transport mechanism is found operative, whereas no transmembrane transport activity was found with 2 and 3, despite the fact that 2 and 3 are also able to bind fluoride via the thiourea moieties. These results demonstrate that the encapsulation of an anionic guest within a cyclic host compound is key to enhancing the anion transport activity and selectivity.

Background: When COVID-19 emerged in China in late 2019, most Chinese university students were home-quarantined to prevent the spread of the virus, considering the great impact of the lockdown on young people habits and their psychological well-being. This study explored the prevalence of post-traumatic stress disorder (PTSD) and its associated factors among Chinese university students who are isolated at home during the COVID-19 pandemic. Method: 4520 participants from five universities in China were surveyed by online questionnaire and the PTSD Checklist—Civilian Version (PCL-C) was adopted as a screening instrument. Results: Exposure to virus was significantly related to PTSD outcomes. The most important predictors for PTSD outcomes were parents’ relationship and the way parents educated, and university-provided psychological counseling was a protective factor against developing PTSD. Conclusions: The COVID-19 pandemic had adverse psychological consequences on Chinese university students who were isolated at home due to the relatively high prevalence rate of PTSD which was reported. Adverse parental relationships and the extreme way parents educate their children could be the major risk factors for PTSD outcomes. Psychological interventions need to be made available to home-quarantined university students, and those in the worst-hit and exposed areas to virus should be given priority focus.

Recently, the present authors used Nevanlinna theory to provide a classification for the Malmquist type difference equations of the form f(z+1)n = R(z, f) (†) that have transcendental meromorphic solutions, where R(z, f) is rational in both arguments. In this paper, we first complete the classification for the case degf (R(z, f)) = n of (†) by identifying a new equation that was left out in our previous work. We will actually derive all the equations in this case based on some new observations on (†). Then, we study the relations between (†) and its differential counterpart (fʹ)n = R(z, f). We show that most autonomous equations, singled out from (†) with n = 2, have a natural continuum limit to either the differential Riccati equation fʹ = a + f² or the differential equation (fʹ)² = a(f² -- τ17#178;)(f² -- τ2²), where a ≠ 0 and i are constants such that τ1² ≠ τ2². The latter second degree differential equation and the symmetric QRT map are derived from each other using the bilinear method and the continuum limit method. [ABSTRACT FROM AUTHOR]