BCAA-producing Clostridium symbiosum promotes colorectal tumorigenesis through the modulation of host cholesterol metabolism.

Identification of potential bacterial players in colorectal tumorigenesis has been a focus of intense research. Herein, we find that Clostridium symbiosum (C. symbiosum) is selectively enriched in tumor tissues of patients with colorectal cancer (CRC) and associated with higher colorectal adenoma recurrence after endoscopic polypectomy. The tumorigenic effect of C. symbiosum is observed in multiple murine models. Single-cell transcriptome profiling along with functional assays demonstrates that C. symbiosum promotes the proliferation of colonic stem cells and enhances cancer stemness. Mechanistically, C. symbiosum intensifies cellular cholesterol synthesis by producing branched-chain amino acids (BCAAs), which sequentially activates Sonic hedgehog signaling. Low dietary BCAA intake or blockade of cholesterol synthesis by statins could partially abrogate the C. symbiosum-induced cell proliferation in vivo and in vitro. Collectively, we reveal C. symbiosum as a bacterial driver of colorectal tumorigenesis, thus identifying a potential target in CRC prediction, prevention, and treatment.

Potential applications of single-incision laparoscopic totally preperitoneal hernioplasty.

BACKGROUND: The totally preperitoneal (TPP) approach is a new concept that was recently introduced. Although the TPP approach combined with single-incision laparoscopic hernia repair has its own advantages, there is little evidence reflecting the characteristics and feasibility of either approach. AIM: To analyze the potential applications of single-incision laparoscopic TPP (SIL-TPP) inguinal hernia hernioplasty for the treatment of inguinal hernias. METHODS: A total of 152 SIL-TPP surgeries were performed at the First Affiliated Hospital of Ningbo University from February 2019 to November 2022. A single-port, named Iconport, and standard laparoscopic instruments were used during the operation. Demographic data, intraoperative parameters and short-term postoperative outcomes were collected and retrospectively analyzed. RESULTS: The demographic data of 152 patients underwent SIL-TPP were shown in Table 1. The average age was 49.5 years (range from 21 to 81 years). The average body mass index was 27.7 kg/m2 (range from 17.7 kg/m2 to 35.6 kg/m2). SIL-TPP were conducted successfully in 147 patients. Three patients were converted to the SIL-transabdominal preperitoneal laparoscopic herniorrhaphy at the initial stage of the study due to a lack of experience. In 2 patients with incisional hernias, an auxiliary operation hole was added during the SIL-TPP procedure, as required for surgery. The mean operative time was 64.5 minutes (range: 36.0-110.0 minutes) for unilateral direct and femoral hernias and 81.6 minutes for indirect hernias (range: 40.0-150.0 minutes). The mean postoperative hospital stay was 3.4 days. CONCLUSION: SIL-TPP is feasible and has advantages for inguinal hernia repair. SIL-TPP has potential benefits for patients with various abdominal wall hernias. Consequently, doctors should be encouraged to actively apply the TPP approach combined with a single incision in their daily work.

The significance of serum SLC7A11 levels in the occurrence of vascular calcification in maintenance peritoneal dialysis patients.

AIM: This research aimed to explore the serum levels of solute carrier family 7 member 11 (SLC7A11) in patients with maintenance peritoneal dialysis (MPD) and its correlation with vascular calcification (VC) and clinical results. METHODS: This present prospective observational cohort study enrolled 189 patients with MPD who were undergoing regular peritoneal dialysis for over 3 months in our hospital from February 2020 to July 2022. The abdominal aortic calcification score was used to assess the VC condition of MPD patients. The serum SLC7A11, interleukin (IL)-6, IL-1ß and C-reactive protein levels were measured by enzyme-linked immunosorbent assay (ELISA). Demographic and clinical statistics were collected. All patients were followed up for 1 year and the overall survival time (OS) of all patients were recorded. All data used SPSS 18.0 for statistical analyses. RESULTS: Patients with moderate/severe calcification in MPD had a longer duration of dialysis, higher serum levels of phosphate (P) and calcium (Ca) and lower serum levels of SLC7A11. Spearman's analysis revealed a negative correlation between serum SLC7A11 levels and the levels of P, Ca and IL-1ß. Additionally, we observed an association between serum SLC7A11 levels and clinical prognosis as well as the extent of VC in MPD patients. Multivariate logistic regression analysis indicated that dialysis duration, SLC7A11, and P were risk factors for VC in MPD patients. CONCLUSION: The serum SLC7A11 levels decreased remarkably in MPD patients with moderate/severe calcification. This study may provide new targets and comprehensive approach to cardiovascular protection in patients with chronic kidney disease.

Identification of risk factors of EGFR-TKIs primary resistance in lung adenocarcinoma patients and construction of a risk predictive model: a case-control study.

Background: Lung cancer is one of the malignancies with the highest incidence and mortality rates. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are recommended as the first-line treatment for patients with EGFR-mutated lung adenocarcinoma (LUAD). However, some patients with EGFR-sensitive mutations develop primary resistance to EGFR-TKIs. This study aims to analyze the clinical characteristics of LUAD patients with primary resistance to EGFR-TKIs, identify independent risk factors for primary resistance, and establish a risk predictive model to provide reference for clinical decision-making. Methods: We collected data from LUAD patients with EGFR-sensitive mutations (19del/21L858R) who were hospitalized in our institution between 2020 and 2022 and received first-generation EGFR-TKIs with follow-up exceeding 6 months. These patients were categorized into primary resistance and sensitive groups based on treatment outcomes. We compared general clinical data, laboratory tests, and tumor-related characteristics between the two groups, analyzed risk factors for primary resistance to EGFR-TKIs, and constructed a risk predictive model. The model's predictive value was comprehensively assessed using receiver operating characteristic (ROC) curves, calibration curves, and decision curves. Results: Serum neuron-specific enolase (NSE) concentration (P=0.03), serum pro-gastrin-releasing peptide (ProGRP) concentration (P=0.01), and Ki67 expression (P<0.001) were identified as independent risk factors for primary resistance to EGFR-TKIs in LUAD. The combined presence of these three risk factors had the highest predictive value [area under the curve (AUC) =0.975, P<0.001]. We constructed a predictive model for the risk of primary resistance to EGFR-TKIs in LUAD patients, incorporating these three parameters, and represented it through a visually interpretable nomogram. The calibration curve of the nomogram demonstrated its strong predictive ability. Further decision curve analysis indicated the model's clinical utility. Conclusions: Based on a single-center retrospective case-control study, we identified serum NSE concentration, ProGRP concentration, and Ki67 expression as independent risk factors for primary resistance to EGFR-TKIs in LUAD patients. We constructed and validated a risk predictive model based on these findings. This predictive model holds promise for clinical application, aiding in the development of personalized treatment strategies and providing a scientific basis for early identification of primary resistance patients.

Characterization and Mechanism of a Novel Rice Protein Peptide (AHVGMSGEEPE) Calcium Chelate in Enhancing Calcium Absorption in Caco-2 Cells.

Rice protein peptides (RPP) are a potentially valuable source of high-quality calcium chelating properties. However, there is a lack of information regarding the calcium-absorption-promoting effect of RPP and its underlying mechanism. The present study adopted molecular docking methodologies to analyze the 10 most potent peptide segments from RPP. Results revealed that the peptide AHVGMSGEEPE (AHV) displayed optimal calcium binding properties (calcium-chelating capacity 55.69 ± 0.66 mg/g). Quantum chemistry analysis revealed that the AHV peptide effectively binds and forms stable complexes with calcium via the carbonyl oxygen atoms in valine at position 3 and the carbonyl of the C-terminal carboxyl group of glutamate at position 11. The spectral analysis results indicated that AHV may bind to calcium through carboxyl oxygen atoms, resulting in a transition from a smooth surface block-like structure to a dense granular structure. Furthermore, this study demonstrated that the 4 mmol/L AHV-Ca chelate (61.75 ± 13.23 µg/well) significantly increases calcium absorption compared to 1 mM CaCl2 (28.57 ± 8.59 µg/well) in the Caco-2 cell monolayer. In terms of mechanisms, the novel peptide-calcium chelate AHV-Ca derived from RPP exerts a cell-level effect by upregulating the expression of TRPV6 calcium-ion-channel-related genes and proteins (TRPV6 and Calbindin-D9k). This study provides a theoretical basis for developing functional foods with the AHV peptide as ingredients to improve calcium absorption.

Arthroscopic inferior leaf meniscectomy of the involved anterior horn in the lateral meniscus horizontal tear via an accessary extreme far anteromedial portal.

BACKGROUND: An accessory extreme far anteromedial portal can improve visualisation and ease inferior leaf meniscectomy in patients with lateral meniscal anterior horn horizontal tears. However, the therapeutic outcomes of adding an accessory extreme far anteromedial portal remain unclear. This study aimed to evaluate the clinical efficacy of adding an accessory extreme far anteromedial portal for treating lateral meniscal horizontal tears involving the anterior horns. METHODS: This retrospective study included 101 patients with anterior horn involvement in lateral meniscal horizontal tears who underwent arthroscopic unstable inferior leaf meniscectomy between January 2016 and December 2020. The pathologies were diagnosed using physical examinations and magnetic resonance imaging. The anterior horn involved in the lateral meniscal horizontal tears was treated using inferior leaf meniscectomy. The primary endpoints were changes in the visual analogue scale, Lysholm, International Knee Documentation Committee, and Tegner scores at the final follow-up. The secondary endpoint was meniscal cure rate at 3 months postoperatively. The preoperative and postoperative functional scores were compared. The occurrence of complications was recorded. RESULTS: All patients were followed up for an average of 4.9 ± 1.2 years (range 2.3-7.5 years). After 4 months, none of the patients experienced pain, weakness, instability, or tenderness in the lateral joint line, achieving an imaging cure rate of 98%. At the final follow-up, significant postoperative improvements were observed in the average values of the visual analogue scale score (3.5 ± 0.7 vs. 0.7 ± 0.6), Lysholm score (62.7 ± 4.4 vs. 91.8 ± 3.1), International Knee Documentation Committee score (61.9 ± 3.7 vs. 91.7 ± 9.5), and Tegner score (2.0 ± 0.7 vs. 6.1 ± 0.7). Excellent Lysholm scores were obtained in 81 patients, and good outcomes were obtained in 18 patients, with an excellent-to-good rate of 98.0%. CONCLUSIONS: Inferior leaf resection via the accessory far anteromedial portal is a safe treatment option for the involved anterior horn in lateral meniscal horizontal tears. This approach enhances visibility and facilitates surgical procedures, with minimal complications.

Construction and validation of a prognostic model for stemness-related genes in lung adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is the most common histological type of lung cancer with poor overall prognosis. Early identification of high-risk patients and individualized treatment can help extend the survival time of patients. This study aimed to construct and validate a prognostic prediction least absolute shrinkage and selection operator (LASSO) model for stemness-related genes in LUAD. Methods: Firstly, LUAD RNA-sequencing data and clinical data were downloaded from The Cancer Genome Atlas (TCGA) database. The tumor stemness index based on mRNA expression (mRNAsi) was calculated, and the relationship between mRNAsi and the survival prognosis as well as clinical features of LUAD patients was analyzed. Then, the weighted gene co-expression network analysis (WGCNA) method was used to screen for gene modules highly correlated with mRNAsi, and functional annotation [Gene Ontology (GO) analysis] and pathway enrichment analysis [Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis] were performed for the selected stemness-related gene module. Furthermore, prognosis-associated genes were determined from the stemness-related genes through univariate Cox analysis, and a prognostic model was constructed using LASSO analysis. Finally, a series of validations including survival curve analysis, receiver operating characteristic (ROC) curve analysis, and risk analysis were conducted for the prognostic model, and nomogram based on the risk model and various clinicopathological features were constructed. Results: LUAD patients with high mRNAsi had a higher mortality rate than those with low mRNAsi. GO analysis showed that stemness-related genes were mainly involved in mRNA processing and extracellular matrix organization, while KEGG analysis revealed their involvement in cell cycle and PI3K-Akt signaling pathways. A prognostic model based on 12 stemness-related genes was constructed using LASSO regression. Validation of the prognostic model demonstrated its good accuracy in predicting the prognosis of LUAD patients. Conclusions: mRNAsi plays an important role in the occurrence and development of LUAD. This study successfully constructed a prognostic prediction LASSO model for stemness-related genes in LUAD, which can serve as a novel prognostic indicator for LUAD and may be an effective complement to the current Tumor Node Metastasis (TNM) clinical staging of LUAD.

Clinical outcomes following direct anterior approach during total hip arthroplasty without hip extension: a retrospective comparative study.

BACKGROUND: Traditional total hip arthroplasty (THA) using the direct anterior approach (DAA) requires a hip extension. This study aimed to compare the clinical outcomes of patients undergoing THA with DAA using either the no hip extension (NHE) or the traditional hip extension (THE) strategy. METHODS: A retrospective analysis of demographics, clinical and radiological outcomes, and occurrence of complications was performed using data from 123 patients treated between January 2020 and November 2021. The patients were categorised into two groups: NHE (84 patients) and THE (39 patients). RESULTS: The NHE group exhibited shorter operative time and had more male participants with higher ages. Comparable outcomes were observed in the visual analogue scale, Harris Hip, and Oxford Hip scores at the final follow-up. Furthermore, complications were observed in the NHE and THE groups, including two and one greater trochanteric fractures and three and one transfusions, respectively. CONCLUSIONS: Compared to the THE, employing the NHE strategy during THA with DAA in elderly and young female patients resulted in comparable clinical outcomes with several advantages, such as favourable surgical time. The NHE method also exhibited good safety and effectiveness. Therefore, the NHE strategy may be a favourable option for elderly and young female patients.

Clinical manifestation, lifestyle, and treatment patterns of chronic erosive gastritis: A multicenter real-world study in China.

BACKGROUND: Although chronic erosive gastritis (CEG) is common, its clinical characteristics have not been fully elucidated. The lack of consensus regarding its treatment has resulted in varied treatment regimens. AIM: To explore the clinical characteristics, treatment patterns, and short-term outcomes in CEG patients in China. METHODS: We recruited patients with chronic non-atrophic or mild-to-moderate atrophic gastritis with erosion based on endoscopy and pathology. Patients and treating physicians completed a questionnaire regarding history, endoscopic findings, and treatment plans as well as a follow-up questionnaire to investigate changes in symptoms after 4 wk of treatment. RESULTS: Three thousand five hundred sixty-three patients from 42 centers across 24 cities in China were included. Epigastric pain (68.0%), abdominal distension (62.6%), and postprandial fullness (47.5%) were the most common presenting symptoms. Gastritis was classified as chronic non-atrophic in 69.9% of patients. Among those with erosive lesions, 72.1% of patients had lesions in the antrum, 51.0% had multiple lesions, and 67.3% had superficial flat lesions. In patients with epigastric pain, the combination of a mucosal protective agent (MPA) and proton pump inhibitor was more effective. For those with postprandial fullness, acid regurgitation, early satiety, or nausea, a MPA appeared more promising. CONCLUSION: CEG is a multifactorial disease which is common in Asian patients and has non-specific symptoms. Gastroscopy may play a major role in its detection and diagnosis. Treatment should be individualized based on symptom profile.

The effect of rice protein-polyphenols covalent and non-covalent interactions on the structure, functionality and in vitro digestion properties of rice protein.

The characteristics of the crosslinking between rice protein (RP) and ferulic acid (FA), gallic acid (GA), or tannin acid (TA) by covalent binding of Laccase and non-covalent binding were evaluated. The RP-polyphenol complexes greatly improved the functionality of RP. The covalent effect with higher polyphenol binding equivalence showed higher emulsion activity than the non-covalent effect. The solubility, and antioxidant activity of covalent binding were higher than that of non-covalent binding in the RP-FA group, but there was a contrasting behavior in the RP-GA group. The RP-FA was most soluble in conjugates, while the RP-GA had the highest solubility in mixtures. It was found that the covalent complexes were more stable in the intestinal tract. The content of polyphenols in the RP-TA group was rapidly increased at the later intestinal digestion, which indicated the high polyphenol-protective effect in this group. Meanwhile, the RP-TA group showed high reducing power but low digestibility.

Global Burden of Lung Cancer Attributable to Household Fine Particulate Matter Pollution in 204 Countries and Territories, 1990 to 2019.

INTRODUCTION: Household particulate matter (PM) air pollution is substantially associated with lung cancer. Nevertheless, the global burden of lung cancer attributable to household PM2.5 is still uncertain. METHODS: In this study, data from the Global Burden and Disease Study 2019 are used to thoroughly assess the burden of lung cancer associated with household PM2.5. RESULTS: The number of deaths and disability-adjusted life-years (DALYs) attributable to household PM2.5 was found to be 0.08 million and 1.94 million, respectively in 2019. Nevertheless, the burden of lung cancer attributable to household PM2.5 decreased from 1990 to 2019. At the sociodemographic index (SDI) district level, the middle SDI region had the most number of lung cancer deaths and DALYs attributable to household PM2.5. Moreover, the burden of lung cancer was mainly distributed in low-SDI regions, such as Sub-Saharan Africa. Conversely, in high-SDI regions, the age-standardized mortality rate and age-standardized DALY rate of lung cancer attributable to household PM2.5 exhibit the most rapid declines. The burden of lung cancer attributable to household PM2.5 is heavier for men than for women. The sex difference is more obvious in the elderly. CONCLUSIONS: The prevalence of lung cancer attributable to household PM2.5 has exhibited a declining trend from 1990 to 2019 owing to a concurrent decline in household PM2.5 exposure.

A methylation-related signature for predicting prognosis and sensitivity to first-line therapies in gastric cancer.

Background: Methylation modification patterns play a crucial role in human cancer progression, especially in gastrointestinal cancers. We aimed to use methylation regulators to classify patients with gastric adenocarcinoma and build a model to predict prognosis, promoting the application of precision medicine. Methods: We obtained RNA sequencing data and clinical data from The Cancer Genome Atlas (TCGA) database (n=335) and Gene Expression Omnibus (GEO) database (n=865). Unsupervised consensus clustering was used to identify subtypes of gastric adenocarcinoma. We performed functional enrichment analysis, immune infiltration analysis, drug sensitivity analysis, and molecular feature analysis to determine the clinical application for different subtypes. The univariate Cox regression analysis and the LASSO regression analysis were subsequently used to identify prognosis-related methylation regulators and construct a risk model. Results: Through unsupervised consensus clustering, patients were divided into two subtypes (cluster A and cluster B) with different clinical outcomes. Cluster B included patients with a better prognosis outcome and who were more likely to respond to immunotherapy. We then successfully built a predictive model and found five methylation-related genes (CHAF1A, CPNE8, PHLDA3, SPARC, and EHF) potentially significant to the prognosis of patients. The 1-, 3-, and 5-year areas under the curve of the risk model were 0.712, 0.696, and 0.759, respectively. The risk score was an independent prognostic factor and had the highest concordance index among common clinical indicators. Meanwhile, the tumor microenvironment, sensitivity of chemotherapeutic drugs, molecular features, and oncogenic dedifferentiation differed significantly across the risk groups and subtypes. Conclusions: We classified patients with gastric adenocarcinoma based on methylation regulators, which has positive implications for first-line clinical treatment. The prognostic model could predict the prognosis of patients and help to promote the development of precision medicine.