Advanced colorectal adenomas are precancerous lesions of colorectal cancer (CRC), and early screening and diagnosis are highly important for improving patient prognosis. However, traditional blood tumor markers have poor diagnostic efficacy for advanced adenoma (AA) and early-stage CRC. We collected serum samples from normal controls, AA patients, and CRC patients (before and 48 h after surgery). Using the enzyme-linked immunosorbent assay method, we compared the serum lipopolysaccharide-binding protein (LBP) and vasodilator-stimulated phosphoprotein (VASP) levels among the three groups. Additionally, we analyzed and compared the serum LBP and VASP levels with the clinicopathological features of the tumors. Finally, we plotted receiver operating characteristic curves, calculated the area under curve and cutoff points, and evaluated the diagnostic efficacy of serum LBP and VASP for AA and CRC patients. Serum LBP and VASP levels were significantly greater in patients with AA and CRC than in healthy controls, and decreased significantly postoperatively compared with preoperatively. Compared with clinicopathological features, serum LBP levels were significantly greater in patients with severe dysplasia in adenomas, whereas serum VASP levels were significantly greater in patients with larger tumors, advanced stages, poorer tumor differentiation, and KRAS gene mutations. Compared with traditional tumor markers, serum LBP and VASP demonstrate good diagnostic efficacy for AA and CRC. Our study innovatively proposes that the serum LBP and VASP proteins could serve as potential novel biomarkers for noninvasive screening of colorectal tumors, with better diagnostic efficacy than traditional blood tumor markers.

Background Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, with a rising incidence among younger adults. Current diagnostic biomarkers lack sufficient sensitivity and specificity, highlighting an urgent need for novel biomarkers. Methods We integrated serum proteomic data from 16 CRC patients and 8 healthy controls with tissue multi-omics data from three external datasets (GSE117606, GSE110223, and GSE110224). Weighted gene co-expression network analysis (WGCNA) was performed to identify CRC-associated modules, followed by support vector machine (SVM) to screen hub proteins. Hub proteins were validated through cross-dataset intersection analysis of differentially expressed genes. Immunohistochemistry was used to assess protein localization, and Receiver operating characteristic (ROC) curve analysis was performed to evaluate diagnostic performance. Results WGCNA identified the MEbrown module as significantly correlated with CRC. GO and KEGG analyses revealed that this module was enriched in pathways related to actin filament organization, focal adhesion, and endocytosis. By intersecting differentially expressed genes from three external datasets and constructing a PPI network, TOP2A was determined as the core molecule, which exhibited differential expression at both the tissue genomic and transcriptomic levels. Immunohistochemistry showed that TOP2A was significantly overexpressed in CRC tissues, with positive signals predominantly localized in the nucleus. ROC curve analysis demonstrated that TOP2A exhibited favorable diagnostic performance across all three datasets, with AUC values all exceeding 0.8. Conclusion This multi-dimensional, multi-dataset integrative strategy successfully identified TOP2A as a potential novel biomarker for CRC. TOP2A exhibited consistent differential expression across serum proteomic, tissue genomic, transcriptomic, and proteomic levels, demonstrating favorable diagnostic performance.

Intermittent fasting (IF) has shown particularly promising short‑term effects in improving metabolic dysfunction‑associated steatotic liver disease (MASLD), although its long‑term efficacy remains unclear. Heterophyllin B (HP‑B), a cyclopeptide compound derived from Pseudostellaria heterophylla, is known for its potent anti‑inflammatory and hypoglycemic properties. However, studies investigating the potential role of HP‑B in the management of MASLD are lacking. In vitro, an OA/PA‑induced lipid accumulation model was established using HepG2/Huh‑7 cells. The therapeutic effects of HP‑B and fasting‑mimicking conditions were evaluated through Cell Counting Kit‑8 assay, Oil Red O staining, reverse transcription‑quantitative PCR, and western blot analysis. For in vivo studies, C57BL/6J mice were fed a high‑fat diet and treated with HP‑B, IF, or their combination. Mechanistic validation was performed via adenovirus‑mediated GLP‑1R knockdown. The present study aimed to explore whether HP‑B can serve as an adjunctive supplement to enhance the benefits of IF in the treatment of MASLD. HepG2 and Huh‑7 liver cancer cells treated with oleic acid/palmitic acid (OA/PA) presented significant lipid accumulation, which was attenuated by HP‑B treatment and fasting. The combination treatment markedly reduced lipid levels and oxidative stress, as well as restored the mitochondrial membrane potential, with a synergistic effect over treatment alone. In addition, the combination of HP‑B and fasting upregulated glucagon‑like peptide‑1 receptor (GLP‑1R) and peroxisome proliferator‑activated receptor gamma coactivator 1‑alpha expression, reversing the OA/PA‑induced decline. In high‑fat diet‑fed mice, the combination treatment reduced hepatic lipid accumulation, decreased liver weight, decreased mouse body weight, and improved biochemical indices of liver function. The beneficial effects of HP‑B and fasting were reversed after silencing GLP‑1R with small interfering RNA or Ad‑GLP‑1R, emphasizing the critical role of GLP‑1R in mediating these protective effects. In conclusion, the synergistic effects of HP‑B and fasting on improving lipid metabolism and mitochondrial function are mediated primarily through the regulation of GLP‑1R, making it a promising therapeutic target for the treatment of MASLD and other lipid metabolism‑related disorders.

OBJECTIVES:To evaluate the effectiveness of a 4-week intervention of time-restricted eating (TRE) alone or in combination with an elimination of ultra-processed foods or vegetarian diet, on body composition, lipid metabolism, and oxidative stress. METHODS:This was a randomized controlled trial including 70 participants comparing three diet groups maintained for a 4-week period: A, TRE alone; B, TRE with elimination of ultra-processed foods; and C, TRE with a vegetarian diet. Per-protocol analyses of body composition, plasma lipid levels, and oxidative stress markers were performed. RESULTS:Compared to baseline, Group B significantly reduced weight (P = 0.02), body mass index, waist and hip circumference, as well as fat ratio, total cholesterol, 4-hydroxynonenal an 8-Iso prostaglandin F 2α (all P < 0.05). Group B also increased high-density lipoprotein cholesterol (P < 0.05) and catalase (P = 0.002). Compared to Group A, Group B was more effective in decreasing body mass index (Δ: -0.1 ± 0.7 vs. -0.2 ± 0.3, respectively, P = 0.041) and waist circumference (Δ: -1.1 ± 4.0 vs. -3.5 ± 4.4, P < 0.001). Compared to Group A and B, the increase in superoxide dismutase (Δ: 12.74 ± 8.34, P < 0.05) and glutathione (Δ: 0.63 ± 0.40, P < 0.05) was significantly greater for Group C. Group C also produced a greater decrease in malondialdehyde (Δ: -0.79 ± 0.28) than the Group A (Δ: -0.32 ± 0.51, P < 0.001) and Group B (Δ: -0.20 ± 0.68, P < 0.001) diets. CONCLUSIONS:Consumption of ultra-processed foods can increase body composition and lipid profile, despite TRE. A vegetarian diet in combination with TRE is effective in reducing oxidative stress injury.

BACKGROUND:Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. The accuracy of noninvasive biomarkers for detecting hepatic steatosis is still limited. AIM:To assess the diagnostic performance of noninvasive steatosis biomarkers in diagnosing NAFLD using magnetic resonance imaging proton density fat fraction (MRI-PDFF) as the gold standard. METHODS:A total of 131 suspected NAFLD patients (60% male, median age 36 years) undergoing MRI-PDFF were consecutively recruited from a tertiary hospital. Steatosis grades determined by MRI-PDFF were classified as none (< 5%), mild (5%-11%), moderate (11%-17%), and severe (≥ 17%). Six steatosis biomarkers were calculated according to clinical parameters and laboratory tests, including fatty liver index, hepatic steatosis index, ZJU index, Framingham steatosis index, triglycerides and glucose index, and visceral adiposity index. The accuracy of these biomarkers in detecting hepatic steatosis was evaluated using the area under the receiver operating characteristic curves (AUCs). The Youden index was used to determine the optimal cut-off for each biomarker. The linear trend analysis of each biomarker across the steatosis grades was conducted by Mantel-Haenszel χ 2 test. Spearman's rank correlation assessed the relationship between steatosis biomarkers and MRI-PDFF. RESULTS:Steatosis grades based on MRI-PDFF prevalence were: None 27%, mild 40%, moderate 15% and severe 18%. Six steatosis biomarkers showed a linear trend across the steatosis grades and a significant positive correlation with MRI-PDFF. The six steatosis biomarkers demonstrated AUCs near 0.90 (range: 0.857-0.912, all P < 0.001) for diagnosing NAFLD by MRI-PDFF ≥ 5%. The optimal cut-offs showed sensitivity between 84.4%-91.7% and specificity between 71.4%-85.7%. The diagnostic performance of these biomarkers in detecting moderate-to-severe and severe steatosis was relatively weaker. CONCLUSION:These noninvasive steatosis biomarkers accurately diagnosed NAFLD and correlated well with MRI-PDFF for detecting NAFLD, but they did not effectively detect moderate or severe steatosis.

Vitamin B12 plays a role in DNA methylation, influencing the 1-carbon cycle; However, its effect on colorectal cancer (CRC) mortality remains uncertain. This study assessed the relationship between vitamin B12 intake and all-cause and cancer-specific mortality among CRC patients. We analyzed data from the NHANES from 1999 to 2018, using multivariable Cox regression, competing risk model, Kaplan-Meier survival curves, and stratified analysis with interaction effects. The studied involved 4,554 cancer patients (mean age 65.8 years, 47.6% males). Results from multivariate Cox regression indicated that each additional 1 mcg/day of dietary vitamin B12 independently increased the risk of all-cause (HR, 1.07; 95% CI: 1.04-1.09, p < 0.001) and cancer-specific mortality (HR, 1.04; 95% CI, 1.02-1.06; p < 0.001). Kaplan-Meier curves indicated a higher risk of all-cause mortality with increased vitamin B12 intake (Log rank p = 0.01). Subgroup analysis suggested that higher vitamin B12 intake correlated with increased all-cause mortality risk, especially in individuals with higher protein (HR, 1.04; 95% CI, 1.02-1.06; p = 0.019) or carbohydrate intake (HR, 1.03; 95% CI, 1.01-1.05; p = 0.04). Thus, higher vitamin B12 intake correlates with increased all-cause and cancer-specific mortality in CRC patients, particularly those with higher protein or carbohydrate intake.

BACKGROUND The 5-year survival rate of patients with colorectal cancer (CRC) in China is only 56.9%, highlighting the need for new therapeutic drugs. Previous studies have shown that matrine exhibits antitumor effects by inducing apoptosis. However, the mechanism by which matrine regulates antiapoptotic proteins in CRC remains unclear. AIM To identify apoptotic proteins from proteomics and investigate the role of matrine in impeding CRC apoptosis by regulating these proteins. METHODS Tumor and adjacent normal tissues were collected from 52 patients with CRC who underwent surgery between January and December 2021. Data-independent acquisition quantitative proteomic analysis was performed to identify differentially expressed apoptotic proteins. The selected apoptotic proteins were identified through their association with tumor-node-metastasis (TNM) stage and prognosis, then confirmed by immunohistochemical (IHC) staining in validation cohort. In vitro, the role of matrine or apoptotic proteins on cancer cells were analyzed. RESULTS Compared to normal tissues, 88 anti-apoptotic proteins from proteomic results were selected. Among them, Shank-associated RH domain interactor (SHARPIN) was identified because of its relationship with TNM stage and overall survival in TCGA database. In the IHC-confirmed cohort, SHARPIN was highly expressed in CRC tissues and localized in the cytoplasm. Higher SHARPIN expression was associated with TNM stage, carbohydrate antigen 153 levels, and gross type compared to low expression. SHARPIN knockdown promoted apoptosis, significantly upregulated the expression of Bcl-2 associated agonist of cell death, Bcl-2 associated X protein, caspase 3, and caspase 8, and downregulated B-cell lymphoma-2 (P < 0.05). Importantly, matrine treatment promoted apoptosis and reversed the proliferation, invasion, and migration of CRC cells by repressing SHARPIN. CONCLUSION SHARPIN was identified as an upregulated anti-apoptotic protein in CRC, and matrine exhibited anticancer effects by downregulating its expression. Thus, matrine appears to be a promising drug for CRC.

BACKGROUND The majority of colorectal cancer (CRC) cases develop from precursor advanced adenoma (AA). With the development of proteomics technologies, blood protein biomarkers have potential applications in the early screening of AA and CRC in the general population. AIM To identify serum protein biomarkers for the early screening of AA and CRC. METHODS We collected 43 serum samples from 8 normal controls (NCs), 19 AA patients and 16 CRC patients at China-Japan Friendship Hospital. Quantitative proteomic analysis was performed using liquid chromatography-mass spectrometry/mass spectrometry and data independent acquisition, and differentially expressed proteins (DEPs) with P-values < 0.05 and absolute fold changes > 1.5 were screened out, followed by bioinformatics analysis. Prognosis was further analyzed based on public databases, and proteins expression in tissues were validated by immunohistochemistry. RESULTS A total of 2132 proteins and 17365 peptides were identified in the serum samples. There were 459 upregulated proteins and 118 downregulated proteins in the NC vs AA group, 289 and 180 in the NC vs CRC group, and 52 and 248 in the AA vs CRC group, respectively. Bioinformatic analysis revealed that these DEPs had different functions and participated in extensive signaling pathways. We also identified DIAPH1, VASP, RAB11B, LBP, SAR1A, TUBGCP5, and DOK3 as important proteins for the progression of AA and CRC. Furthermore, VASP (P < 0.01), LBP (P = 0.01), TUBGCP5 (P < 0.01), and DOK3 (P < 0.01) were associated with a poor prognosis. In addition, we propose that LBP and VASP may be more promising protein biomarkers for the early screening of colorectal tumors. CONCLUSION Our study elucidated the serum proteomic profiles of AA and CRC patients, and the identified proteins, such as LBP and VASP, may contribute to the early detection of AA and CRC.

ObjectivesSessile serrated lesions (SSLs) are precursors of sporadic colorectal cancer (CRC) and have distinct characteristics compared with conventional adenomas (CAs). Several lifestyle and environmental factors may play critical roles in the development of advanced lesions. Our aim is to describe the features of SSLs and CAs and further explore risk factors for advanced lesions.MethodsThis is an observational study that collected demographic, endoscopic, and histological data from the China-Japan Friendship Hospital among the inpatient population with pathologically reported as SSL or CA between 2015 and 2022. We analyzed the clinicopathology and endoscopic differences between SSL alone, CA alone, and synchronous SSL+CA groups, and identified risk factors using multiple regression analysis.ResultsA total of 9236 polyps from 6598 patients were included in the cohort. Patients with SSL+CA were more likely to be older (p=0.008), while individuals with SSL alone had a higher proportion of early-onset polyps (p<0.001), and SSLs were more common in advanced polyps than CAs (p<0.001). A greater proportion of advanced polyps in the SSL and CA groups were diagnosed as Yamada III, Yamada IV, and laterally spreading tumor (p=0.002, p<0.001, respectively), and multiple SSLs and CAs were more represented in nonadvanced polyps than in advanced polyps. In multiple regression analysis, older patients were more likely to develop advanced SSLs (aOR 1.05, 95% CI 1.02-1.09, p=0.005).ConclusionSSLs and CAs have diverse demographic, endoscopic, and histological characteristics, and their advanced lesions share different risk factors, which advances the understanding of the etiology and progression of SSLs.

Introduction: Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common chronic liver disease, which is usually associated with type 2 diabetes mellitus (T2DM) and obesity. However, the incidence of MALFD in non-obese individuals without T2DM is increasing, and the pathogenesis is unclear. Serum uric acid to creatinine ratio (sUA/Cr) can reflect overall metabolic status. This study aims to observe the association between sUA/Cr and MAFLD in non-obese individuals without T2DM.Methods: A total of 21,996 individuals were included in this study. The subjects were divided into four subgroups: non-obese patients without T2DM, obese patients without T2DM, non-obese patients with T2DM, and obese patients with T2DM. Logistic regression analyzed the correlation between sUA/Cr and MAFLD subgroups. Receiver operating characteristics analyzed the predictive value of sUA/Cr for MAFLD subgroups. The stratified analyses by sex and age were performed.Results: Non-obese MAFLD individuals without T2DM had higher sUA/Cr levels than their counterparts. sUA/Cr was significantly correlated positively with MAFLD in non-obese patients. Similar results were observed in both males and females and in populations at all age stages (all p<0.01). sUA/Cr was capable of discriminating MAFLD in non-obese individuals without T2DM (AUC: 0.667), especially for patients over 60 years old (AUC: 0.704).Conclusion: The sUA/Cr ratio was correlated with MAFLD in non-obese patients without T2DM. The predictive value of sUA/Cr for MAFLD was observed. Hence, the sUA/Cr ratio might be given more concern for the risk of MAFLD in non-obese individuals without T2DM.

BACKGROUND AND STUDY AIMS:Metabolic dysfunction-associated fatty liver disease (MAFLD) has become the most common cause of chronic liver disease worldwide. Diet plays a critical role in the prevention and treatment of MAFLD. Our hypothesis was that the intake of some macronutrients, vitamins, or mineral elements is associated with MAFLD. PATIENTS AND METHODS:Patients with MAFLD can be diagnosed based on the evidence of hepatic steatosis and if they meet any of the three additional criteria of overweight/obesity, diabetes mellitus, or metabolic dysregulation. Diets were recorded using photographs and diaries of meals for seven consecutive days. The consumed dietary composition was compared with the recommended intake according to the China Food Composition Tables (Standard Edition) version 2019 and the Chinese Dietary Reference Intakes version 2013, and its association with MAFLD was assessed by logistical regression analyses. RESULTS:A total of 229 MAFLD patients and 148 healthy controls were included in this study. MAFLD patients, compared with that by non-MAFLD participants, consumed more polyunsaturated fatty acids (PUFAs) (p < 0.001), vitamin E (p < 0.001), and iron (p = 0.008). The intake of PUFAs (OR = 1.070, 95 % CI: 1.017-1.127, p = 0.009) and vitamin E (OR = 1.100, 95 % CI: 1.018-1.190, p = 0.016) was positively associated with MAFLD. In addition, the percentages of individuals who consumed PUFAs (p = 0.006), vitamin E (p < 0.001), or iron (p = 0.046) above the recommended intake were higher among the individuals with MAFLD. Daily intake of PUFAs > 11 % (OR = 2.328, 95 % CI: 1.290-4.201, p = 0.005) and vitamin E > 14 mg (OR = 2.189, 95 % CI: 1.153-4.158, p = 0.017) was positively correlated with MAFLD. CONCLUSIONS:Patients with MAFLD consumed more PUFAs, vitamin E, and iron in their daily diet. Excessive consumption of PUFAs and vitamin E might be independent risk factors for the incidence of MAFLD.

This study aimed to comprehensively and methodically evaluate the correlation between cognitive impairment and indoor air pollution from solid fuel used for cooking/heating. PubMed, Web of Science, EMBASE, and Cochrane Library databases were searched up to December January 2023. 13 studies from three countries with a total of 277,001 participants were enrolled. A negative correlation was discovered between solid fuel usage for cooking and total cognitive score (beta=-0.73, 95 % CI: -0.90 to -0.55) and episodic memory score (beta=-0.23, 95 % CI: -0.30 to -0.17). Household solid fuel usage for cooking was considerably associated with a raised risk of cognitive impairment (HR=1.31, 95 % CI: 1.09-1.57) and cognitive decline (HR=1.24, 95 % CI: 1.18-1.30). Compared to continuous solid fuel use for cooking, sustained use of clean fuel and switching from solid fuel to clean fuel were associated with a lower risk of cognitive decline (OR=0.55, 95 % CI: 0.42-0.73; OR=0.81, 95 % CI: 0.71-0.93). A negative association was found between solid fuel usage for heating and total cognitive score (beta=-0.43, 95 % CI: -0.59 to -0.26) and episodic memory score (beta=-0.22, 95 % CI: -0.34 to -0.10). Our research provided evidence that exposure to indoor air pollution from solid fuel is a potential cause of cognitive impairment and cognitive decline. Making the switch from solid fuels to cleaner fuels could be an important step in preventing cognitive impairment in the elderly.

Homologous recombination defects (HRD) render cells fail to repair DNA double-strand break (DSB), which causes synthetic lethality in these cells with punch by poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi). Here, we reveal a receptor tyrosine kinase, AXL, whose inhibition leads to HRD in hepatocellular carcinoma (HCC) cells. AXL is upregulated in HCC tumors, which is positively correlated with low survival rates. AXL knockdown or AXL inhibition by bemcentinib reduces HR efficiency in HCC cells, and AXL plays its role in HR repair through its kinase activity. Furthermore, we find that AXL interacts with RPA2, enhancing the recruitment of RPA2 to DNA damage sites. Mechanistically, AXL promotes the tyrosinization of RPA2 at tyrosine 9, promoting the phosphorylation of CHK1, thereby strengthens the HR repair ability in HCC cells to resist DNA damage. In conclusion, our results reveal that AXL is a promising therapeutic biomarker for HCC patients, and present that targeting AXL-RPA2-CHK1 pathway together with PARP inhibitor will be effective therapeutic strategy in HCC.

Purpose: It is unclear how the Chinese Visceral Adiposity Index (cVAI) relates to metabolic dysfunction-associated fatty liver disease (MAFLD) and alanine aminotransferase (ALT) in nonobese individuals. In this study, we evaluated the ability of the cVAI to predict MAFLD and elevated ALT in nonobese participants. Methods: This cross-sectional study recruited 541 nonobese subjects from March 2019 to January 2022 with the age range of 18-80 years. Hepatic steatosis was diagnosed by ultrasound. Participants were divided into four groups according to cVAI quartiles. To assess the associations between cVAI and MAFLD and elevated ALT, multivariate logistic regression was used. Receiver operating characteristic (ROC) curves were generated to evaluate the ability of the cVAI to predict MAFLD and elevated ALT. Results: Compared to the group with the lowest cVAI, the group with the highest cVAI was positively associated with nonobese MAFLD [16.173 (4.082-64.073), P < 0.001] and elevated ALT [8.463 (2.859-25.049), P < 0.001]. The area under the ROC curve (AUC) of the cVAI was greater than that of WC, waist-to-height ratio, or BMI for predicting nonobese MAFLD in the male, female, > 38 and <= 38 years old subgroups (P < 0.05), respectively. In addition, the ability of the cVAI to predict MAFLD was better in females, young individuals, and individuals with a higher education level (P < 0.05). The cVAI also had good predictive ability for elevated ALT levels [0.655 (0.602-0.708)], particularly in females, young people, and highly educated participants. Furthermore, the cVAI was strongly positively correlated with the liver fibrosis score (P < 0.05) and was also a strong indicator of concomitant metabolic syndrome in nonobese MAFLD patients [AUC = 0.688 (0.612-0.763)]. Conclusion: The cVAI was strongly related to nonobese MAFLD and elevated ALT. The cVAI may be a reliable and accessible predictor of nonobese MAFLD and elevated ALT.

OBJECTIVES:Left-sided colon cancer (LSCC) and right-sided colon cancer (RSCC) have shown distinct clinical and prognostic features. We investigated the effect of adjuvant chemotherapy (ACT) on cause-specific survival (CSS) in patients with stage II LSCC and RSCC. METHODS:Using the Surveillance, Epidemiology and End Results (SEER) database, a cohort of patients with stage II colon cancer, aged between 20 and 49 years was identified. Both Cox proportional hazards regression and Kaplan-Meier survival analysis as well as propensity score matching were used. RESULTS:Overall, 5633 patients were eligible. Patients with RSCC were more likely to be male, black, and younger, with a poor grade and histologic type, and were more likely to have more regional nodes examined and larger tumor size. After propensity score matching, CSS was significantly superior in patients with RSCC compared to those with LSCC (Hazard Ratio (HR): 0.80, 95% CI: 0.68-0.95, P =0.01). However, no survival benefit was observed for patients with LSCC after ACT (HR: 1.10, 95% CI: 0.90-1.35, P =0.35), and surprisingly, ACT was found to do more harm than good in patients with RSCC (HR: 1.31, 95% CI: 1.05-1.63, P =0.02). Even among patients with high-risk features such as T4 stage and regional nodes examined<12 in both groups, ACT still did not improve CSS except for T4 stage LSCC (HR: 0.65, 95% CI: 0.44-0.97, P =0.02). CONCLUSIONS:The results of this analysis indicate that the prognosis of RSCC is better than that of LSCC in stage II colon cancer, and ACT did not improve CSS in patients with either LSCC or RSCC. Even in patients with parts of high-risk features, ACT still did not improve CSS, except for T4 stage LSCC.

BACKGROUND:microRNA-627-5p (miR-627-5p) dysregulation has been observed in several cancer types, such as hepatocellular carcinoma, oral squamous cell carcinoma, glioblastoma multiforme, and gastric cancer. The biological function of miR-627-5p in colorectal cancer (CRC) growth and metastasis is yet unclear.AIM:To investigate the effects of miR-627-5p on the malignant biological properties of colorectal malignant tumour cells by targeting Wnt2.METHODS:The levels of miR-627-5p in colorectal tumour tissues were assessed in Gene Expression Omnibus datasets. In order to identify Wnt2 transcript expression in CRC tissues, quantitative real-time polymerase chain reaction (qRT-PCR) analysis was used. Luciferase reporter tests were used to explore whether miR-627-5p might potentially target Wnt2. Wnt2 transcript and protein levels were detected in CRC cells with high miR-627-5p expression. To learn more about how miR-627-5p affects CRC development, migration, apoptosis, and invasion, functional experiments were conducted. Cotransfection with the overexpression vector of Wnt2 and miR-627-5p mimics was utilized to verify whether overexpression of Wnt2 could cancel the impact of miR-627-5p in CRC. Western blot and qRT-PCR were conducted to investigate the effects of miR-627-5p on the Wnt/β-catenin signalling pathway.RESULTS:miR-627-5p was notably decreased in colorectal tumour tissues, while the gene level of Wnt2 was notably upregulated. A dual luciferase reporter assay revealed that miR-627-5p specifically targets the 3'-untranslated regions of Wnt2 and miR-627-5p upregulation markedly reduced the protein and gene expression of Wnt2 in CRC cells. In vitro gain-of-function assays displayed that miR-627-5p overexpression decreased CRC cells' capabilities to invade, move, and remain viable while increasing apoptosis. Wnt2 overexpression could reverse the suppressive functions of miR-627-5p. Moreover, upregulation of miR-627-5p suppressed the transcript and protein levels of the downstream target factors in the canonical Wnt/β-catenin signalling, such as c-myc, CD44, β-catenin, and cyclinD1.CONCLUSION:miR-627-5p acts as a critical inhibitory factor in CRC, possibly by directly targeting Wnt2 and negatively modulating the Wnt/β-catenin signalling, revealing that miR-627-5p could be a possible treatment target for CRC.

目的:探究非酒精性脂肪性肝病(NAFLD)患者中医证型与CT值、实验室指标的关系.方法:于2021年1月至2021年10月在北京某三甲医院体检中心招募NAFLD患者129例,按照制定的标准化问卷调查表和体检报告收集人口学信息和实验室指标,并进行中医证型分析.结果:共纳入NAFLD患者129例,平均年龄(46.2±9.5)岁.在4种证型中,湿热蕴结证(52.71％)最为常见,其余依次为痰瘀互结证(28.68％)、肝郁脾虚证(10.08％)和痰浊内阻证(8.53％).痰瘀互结证患者肝脏CT值[39.1(33.0,41.5)]显著低于湿热蕴结患者[44.1(34.6,46.4)]和痰浊内阻证患者[47.4(37.8,50.4)],均P<0.05.痰瘀互结证患者肝脾CT比值[0.72(0.60,0.79)]显著低于肝郁脾虚证患者[0.80(0.76,0.89)]、湿热蕴结证患者[0.81(0.67,0.88)]和痰浊内阻证患者[0.86(0.72,0.88)],均P<0.05.不同中医证型NAFLD患者的PLT、Urea、HDL-C水平存在统计学差异.结论:NAFLD患者以湿热蕴结证最为常见;与其他证型患者相比,痰瘀互结证患者脂肪变性程度更重.将中医证型与CT值和实验室指标相结合,有助于从中西医结合的角度更全面的认识NAFLD.

HUA is an independent risk factor for MAFLD in nonobese patients without T 2 DM. The association of HUA with MAFLD in nonobese patients without T 2 DM increased gradually with aging, especially in those over 40 yr old. In nonobese patients without T 2 DM, univariate analysis showed that females with HUA had a higher risk of MAFLD than males. However, the difference was narrowed after adjustment for confounders.

目的 探讨功能性便秘(FC)患者的饮食因素影响.方法 纳入 2017 年 1 月至 2020 年 12 月就诊于中日友好医院中医脾胃病科及消化科门诊或病房的FC患者 135 例(FC组)和健康志愿者90 例(对照组),签署知情同意书后填写近 1 年饮食调查问卷,通过多种统计学方法分析得出饮食与FC的相关性.结果 FC组进食干炒类、乳制品得分显著高于对照组,而水、蔬菜、水果、粗粮、豆制品得分显著低于对照组;油炸类、烧烤类、干炒类、蛋类、乳制品、咖啡与FC呈正相关,且乳制品相关系数最高(rs=0.4),水、蔬菜、水果、粗粮、豆制品与FC呈负相关,且蔬菜相关系数最高(rs=-0.4);经调整性别、年龄混杂因素后,多因素逻辑回归分析得出烧烤类(OR=1.20)、干炒类(OR=1.12)、乳制品(OR=1.37)与FC呈正相关,水(OR =0.53)、蔬菜(OR =0.75)、水果(OR=0.59)、粗粮(OR=0.71)、豆制品(OR=0.77)与FC呈负相关.结论 多饮水及多进食蔬菜、水果、粗粮、豆制品,尽量少食烧烤类、干炒类、乳制品可能是改善FC的有效食疗方法.

BACKGROUND:Colorectal cancer (CRC) is the second leading cause of cancer-related death, with high morbidity worldwide. There is an urgent need to find reliable diagnostic biomarkers of CRC and explore the underlying molecular mechanisms. Exosomes are involved in intercellular communication and participate in multiple pathological processes, serving as an important part of the tumor microenvironment.AIM:To investigate the proteomic characteristics of CRC tumor-derived exosomes and to identify candidate exosomal protein markers for CRC.METHODS:In this study, 10 patients over 50 years old who were diagnosed with moderately differentiated adenocarcinoma were recruited. We paired CRC tissues and adjacent normal intestinal tissues (> 5 cm) to form the experimental and control groups. Purified exosomes were extracted separately from each tissue sample. Data-independent acquisition mass spectrometry was implemented in 8 matched samples of exosomes to explore the proteomic expression profiles, and differentially expressed proteins (DEPs) were screened by bioinformatics analysis. Promising exosomal proteins were verified using parallel reaction monitoring (PRM) analysis in 10 matched exosome samples.RESULTS:A total of 1393 proteins were identified in the CRC tissue group, 1304 proteins were identified in the adjacent tissue group, and 283 proteins were significantly differentially expressed between them. Enrichment analysis revealed that DEPs were involved in multiple biological processes related to cytoskeleton construction, cell movement and migration, immune response, tumor growth and telomere metabolism, as well as ECM-receptor interaction, focal adhesion and mTOR signaling pathways. Six differentially expressed exosomal proteins (NHP2, OLFM4, TOP1, SAMP, TAGL and TRIM28) were validated by PRM analysis and evaluated by receiver operating characteristic curve (ROC) analysis. The area under the ROC curve was 0.93, 0.96, 0.97, 0.78, 0.75, and 0.88 (P < 0.05) for NHP2, OLFM4, TOP1, SAMP, TAGL, and TRIM28, respectively, indicating their good ability to distinguish CRC tissues from adjacent intestinal tissues.CONCLUSION:In our study, comprehensive proteomic profiles were obtained for CRC tissue exosomes. Six exosomal proteins, NHP2, OLFM4, TOP1, SAMP, TAGL and TRIM28, may be promising diagnostic markers and effective therapeutic targets for CRC, but further experimental investigation is needed.