Assessment of risk factors of lymph node metastasis and prognosis of Siewert II/III adenocarcinoma of esophagogastric junction: A retrospective study.

Adenocarcinoma of the esophagogastric junction (AEG) has a high incidence, and the extent of lymph node dissection (LND) and its impact on prognosis remain controversial. This study aimed to explore the risk factors for lymph node metastasis (LNM) and prognosis in Siewert II/III AEG patients. A retrospective review of 239 Siewert II/III AEG patients surgically treated at Beijing Friendship Hospital from July 2013 to December 2022 was conducted. Preoperative staging was conducted via endoscopy, ultrasound gastroscopy, CT, and biopsy. Depending on the stage, patients received radical gastrectomy with LND and chemotherapy. Clinicopathological data were collected, and survival was monitored semiannually until November 2023. Utilizing logistic regression for data analysis and Cox regression for survival studies, multivariate analysis identified infiltration depth (OR = 0.038, 95% CI: 0.011-0.139, P < .001), tumor deposit (OR = 0.101, 95% CI: 0.011-0.904, P = .040), and intravascular cancer embolus (OR = 0.234, 95% CI: 0.108-0.507, P < .001) as independent predictors of LNM. Lymph nodes No. 1, 2, 3, 4, 7, 10, and 11 were more prone to metastasis in the abdominal cavity. Notably, Siewert III AEG patients showed a higher metastatic rate in nodes No. 5 and No. 6 compared to Siewert II. Mediastinal LNM was predominantly found in nodes No. 110 and No. 111 for Siewert II AEG, with rates of 5.45% and 3.64%, respectively. A 3-year survival analysis underscored LNM as a significant prognostic factor (P = .001). Siewert II AEG patients should undergo removal of both celiac and mediastinal lymph nodes, specifically nodes No. 1, 2, 3, 4, 7, 10, 11, 110, and 111. Dissection of nodes No. 5 and No. 6 is not indicated for these patients. In contrast, Siewert III AEG patients do not require mediastinal LND, but pyloric lymphadenectomy for nodes No. 5 and No. 6 is essential. The presence of LNM is associated with poorer long-term prognosis. Perioperative chemotherapy may offer a survival advantage for AEG patients.

Investigating biomechanical alterations and emptying patterns after various gastrojejunostomy strategy.

Gastrojejunostomy is a prominent approach in managing distal gastric cancer that is unresectable due to gastric outlet obstruction (GOO). Research has demonstrated that stomach-partitioning gastrojejunostomy (SPGJ) exhibits superior clinical efficacy compared to conventional gastrojejunostomy (CGJ), however, the underlying mechanism of this phenomenon remains elusive. This study constructed 3D models of the SPGJ and CGJ based on the computed tomography (CT) images obtained from a patient diagnosed with distal gastric cancer. The biomechanical patterns of these procedures in the digestive system were subsequently compared through numerical simulations and in vitro experiments. The results of the numerical simulation demonstrated that the model following SPGJ promoted the discharge of food through the anastomotic orifice and into the lower jejunum. Furthermore, a decrease in passage size after partitioning, the low-level velocity of esophageal, and an increase in contents viscosity effectively inhibited the flow through the passage to the pylorus, ultimately reducing stimulation to tumor. The study also revealed that favorable gastric emptying is associated with a smaller passage and faster inlet velocity, and that lower contents viscosity. ​The experimental findings conducted in vitro demonstrated that SPGJ exhibited superior efficacy in obstructing the flow near the pylorus in comparison to CGJ. Moreover, a decrease in passage size correlates with a reduction in fluid flow towards the pylorus. These results provide the foundation of theory and practice for the surgical management of patients with GOO resulting from unresectable distal gastric cancer, and have potential implications for clinical interventions.

DNMT1 regulates hypermethylation and silences hsa_circ_401351 in hydroquinone-induced malignant TK6 cells.

BACKGROUND: Benzene and its metabolite hydroquinone (HQ) are widely used in daily life, and long-term exposure to benzene or HQ can induce acute myeloid leukemia (AML). Circular RNAs (circRNAs) are mostly produced by reverse splicing of gene exon mRNA precursors. The modulation of circRNA expression is connected to leukemia progression; however, the molecular mechanism is still unknown. MATERIALS AND METHODS: In this study, the cells were divided into four groups: PBS control group (PBS-TK6), TK6 malignantly transformed cells induced by 10.0 µmol/L HQ (HQ-TK6), and HQ-TK6 cells treated with 5 µmol/L 5-AzaC (DNA methyltransferase inhibitor) for 24 h (HQ + 5-AzaC). HQ-TK6 cells were treated with 200 nmol/L TSA (histone deacetylation inhibitor) for 24 h (HQ + TSA). qRT-PCR was used to identify the differential hsa_circ_401351 expression between the four groups. We further determined the hsa_circ_401351 promoter methylation level with methylation-specific PCR. DNMT1 and DNMT3b were knocked down by CRISPR/Cas9 to elucidate the specific molecular mechanism of hsa_circ_401351 in HQ-TK6 cells. CCK-8 and flow cytometry detected cell proliferation and apoptosis, respectively, after hsa_circ_401351 was overexpressed in HQ-TK6 cells. RESULTS: Compared with the PBS-TK6 group, the expression of hsa_circ_401351 was found to be lower in the HQ-TK6 group. Nevertheless, treatment with 5-AzaC or TSA increased hsa_circ_401351 expression, with the upregulation being more pronounced in the TSA group. The expression of hsa_circ_401351 in the DNMT1 knockdown group was dramatically increased by 50% compared to that in the control group, and the DNA methylation level of the hsa_circ_401351 promoter region was decreased. When hsa_circ_401351 was overexpressed, HQ-TK6 cell proliferation was significantly slowed after 48 h compared with the control group. Flow cytometry showed that cells were mainly arrested in G1 phase, and apoptosis was significantly enhanced. Similarly, qRT-PCR and Western blot data showed significant reductions in Caspase-3 mRNA and protein production, and Bcl-2 mRNA levels were also elevated. CONCLUSIONS: Overall, our research showed that elevated DNMT1 expression in HQ-TK6 cells increased methylation levels and decreased expression of the hsa_circ_401351 promoter region, limiting its ability to suppress HQ-TK6 cell growth and enhance apoptosis.

Exploring the safety and efficacy of stomach-partitioning gastrojejunostomy with distal selective vagotomy versus conventional gastrojejunostomy with highly selective vagotomy for treating benign gastric outlet obstruction: study protocol for a randomised controlled trial.

INTRODUCTION: Benign gastric outlet obstruction (BGOO) severely impacts the quality of life of patients. The main treatment methods for BGOO include surgery and endoscopy, but both have significant drawbacks. Therefore, this study aims to explore the safety and efficacy of a new technique, to develop a new option for treating BGOO. METHODS AND ANALYSIS: This is an ongoing prospective, single-centre, single-blind randomised controlled trial. The study will be conducted from January 2022 to December 2025, and 50 patients will be enrolled. The participants will be randomly assigned in a 1:1 ratio to either the experimental (stomach-partitioning gastrojejunostomy with distal selective vagotomy) or control groups (conventional gastrojejunostomy with highly selective vagotomy). We will collect baseline characteristics, laboratory tests, auxiliary examinations, operation, postoperative conditions and follow-up data. Follow-up will last for 3 years. The main outcome is the incidence of delayed gastric emptying within 30 days after surgery. Secondary outcomes include the efficacy indicator (consisting of serum gastrin level, pepsinogen level, 13C breath test, gastrointestinal quality of life index, operation time, blood loss and postoperative recovery), a safety evaluation index (consisting of complications and mortality within 30 days after surgery) and follow-up data (consisting of the incidence of primary ulcer progression in 3 years after surgery, and the gastroscopy results in 1 and 3 years after surgery). ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee of Beijing Friendship Hospital, Capital Medical University (no. 2021-P2-274-02). The study conformed to the provisions of the Declaration of Helsinki (as revised in 2013). Written informed consent will be obtained prior to study enrolment. The results of this study will be published in peer-reviewed publications. TRIAL REGISTRATION NUMBER: ChiCTR2100052197.

Increased DNMT1 Involvement in the Activation of LO2 Cell Death Induced by Silver Nanoparticles via Promoting TFEB-Dependent Autophagy.

The accumulation of exogenous silver nanoparticles (AgNPs) will terminally bring about liver injury, including cell death, where DNA methylation tends to be a crucial epigenetic modulator. The change in the cell autophagy level verified to be closely associated with hepatocyte death has been followed with wide interest. But the molecular toxicological mechanisms of AgNPs in relation to DNA methylation, autophagy, and cell death remain inconclusive. To address the issue above, in LO2 cells treated with increasing concentrations of AgNPs (0, 5, 10, and 20 µg/mL), a cell cytotoxicity assay was performed to analyze the level of cell death, which also helped to choose an optimal concentration for next experiments. An immunofluorescence assay was used to determine the autophagic flux as well as TFEB translocation, with qRT-PCR and western blot being used to analyze the expression level of autophagy-related genes and proteins. According to our findings, in the determination of cell viability, 20 µg/mL (AgNPs) was adopted as the best working concentration. LO2 cell death, autophagy, and TFEB nuclear translocation were induced by AgNPs, which could be inhibited by lysosome inhibitor chloroquine (CQ) or siRNA specific for TFEB. Moreover, AgNP exposure led to DNA hypermethylation, with DNMT1 taking part mainly, which could be obviously prevented by 5-Aza-2'-deoxycytidine (5-AzaC) or trichostatin A (TSA) treatment or DNMT1 knockout in LO2 cells. Our studies suggest that through TFEB-dependent cell autophagy, increased DNMT1 may facilitate cell death induced by AgNPs.

Identification of differentially expressed genes and pathways in BEAS-2B cells upon long-term exposure to particulate matter (PM2.5) from biomass combustion using bioinformatics analysis.

BACKGROUND: Long-term exposure to PM2.5 from burning domestic substances has been linked to an increased risk of lung disease, but the underlying mechanisms are unclear. This study is to explore the hub genes and pathways involved in PM2.5 toxicity in human bronchial epithelial BEAS-2B cells. METHODS: The GSE158954 dataset is downloaded from the GEO database. Differentially expressed genes (DEGs) were screened using the limma package in RStudio (version 4.2.1). In addition, DEGs analysis was performed by Gene Ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. A protein-protein interaction (PPI) network was constructed, MCODE plug-in and the cytoHubba plug-in in Cytoscape software was used to identify the hub genes. Finally, CytoHubba and DEGs were used to integrate the hub genes, and preliminary validation was performed by comparing the toxicology genomics database (CTD). Differential immune cell infiltration was investigated using the CIBERSORT algorithm. RESULTS: A total of 135 DEGs were identified, of which 57 were up-regulated and 78 were down-regulated. Functional enrichment analyses in the GO and KEGG indicated the potential involvement of DEGs was mainly enriched in the regulation of endopeptidase activity and influenza A. Gene Set Enrichment Analysis revealed that Chemical Carcinogenesis - DNA adducts were remarkably enriched in PM2.5 groups. 53 nodes and 198 edges composed the PPI network. Besides, 5 direct-acting genes were filtered at the intersection of cytohubba plug-in, MCODE plug-in and CTD database. There is a decreasing trend of dendritic cells resting after BEAS-2B cells long-term exposure to PM2.5. CONCLUSIONS: The identified DEGs, modules, pathways, and hub genes provide clues and shed light on the potential molecular mechanisms of BEAS-2B cells upon long-term exposure to PM2.5.

Safety and efficacy of augmented-rectangle technique versus delta-shaped anastomosis for treating gastric cancer in total laparoscopic distal gastrectomy.

PURPOSE: This study aimed to evaluate the safety and efficacy of augmented-rectangle technique (ART) versus delta-shaped anastomosis (DA) for treating gastric cancer in total laparoscopic distal gastrectomy. METHODS: In total, 99 patients with distal gastric cancer who underwent ART (n = 60) or DA (n = 39) were considered. Operative data, postoperative recovery, complications, quality of life, and endoscopic findings of both groups were compared. RESULTS: The ART group had faster postoperative recovery than the DA group, and was better than DA regarding complications. The mode of reconstruction remained an independent predictor of complications, but not postoperative recovery. Dumping syndrome occurred in 3 (5.0%) and 2 patients (5.1%) of ART and DA groups within 30 days after surgery, and 3 (5.0%) and 2 patients (5.1%) 1 year after surgery. Regarding global health status on the EORTC-QLQ-C30 scale, the ART group had better outcomes than the DA group. Gastritis occurred in 38 (63.3%) and 27 (69.3%) patients of ART and DA groups, respectively. Residual food occurred in 8 (13.3%) and 11 (28.2%) patients of ART and DA groups. Reflux esophagitis occurred in 5 (8.3%) and 4 (10.3%) patients of ART and DA groups. Further, bile reflux occurred in 8 (13.3%) and 4 (10.3%) patients of ART and DA groups. CONCLUSIONS: ART has similar advantages to DA for total laparoscopic reconstruction and is superior to DA regarding the incidence of complications, complication grade, and global health status. Furthermore, ART may have potential advantages in postoperative recovery and anastomotic stenosis.

Predictive performance of radiomics for peritoneal metastasis in patients with gastric cancer: a meta-analysis and radiomics quality assessment.

PURPOSE: The purpose of this meta-analysis is to systematically review the diagnostic performance of radiomic techniques in predicting peritoneal metastasis in patients with gastric cancer, and to evaluate the quality of current research. METHODS: We searched PubMed, Web of Science, EBSCO, Embase, and Cochrane databases for relevant studies up to April 3, 2023. Data extraction and quality evaluation were performed by two independent reviewers. Then we performed statistical analysis, including plotting the forest plot and summary receiver operating characteristic (SROC) curve, and source of heterogeneity analysis, through the MIDAS module in Stata 15. We performed meta-regression and subgroup analyses to analyze the sources of heterogeneity. Using the QUADAS-2 scale and the RQS scale to assess the quality of retrieved studies. RESULTS: Ten studies with 6199 patients were finally included in our meta-analysis. Pooled sensitivity and specificity were 0.77 (95% confidence interval [CI]: 0.66, 0.86), and 0.88 (95% CI 0.80, 0.93), respectively. The overall AUC was 0.89 (95% CI 0.86, 0.92). The heterogeneity of this meta-analysis was high, with I2 = 88% (95% CI 75,100). The result of meta-regression showed that QUADAS-2 results, RQS results and machine learning method led to heterogeneity in sensitivity and specificity (P < 0.05). Furthermore, the image segmentation area and the presence or absence of combined clinical factors were associated with sensitivity heterogeneity and specificity heterogeneity, respectively. CONCLUSION: Undoubtedly, radiomics has potential value in diagnosing peritoneal metastasis of gastric cancer, but the quality of current research is inconsistent, and more standardized and high-quality research is still needed in the future to achieve the transformation of radiomics results into clinical applications.

Improving the decorative performance of UV-curable coatings with iridescent cellulose nanocrystal film.

Cellulose nanocrystals (CNC) possess remarkable mechanical properties, a high aspect ratio, a large specific surface area, and a unique nanostructure, making them a popular choice in various fields. In this study, a CNC suspension was prepared through acid hydrolysis, and subsequently, a film exhibiting iridescence and chiral nematic structure was formed on the cured UV-WA surface via evaporation-induced self-assembly. The mean diameter and length of CNC were determined to be 25.1-33.3 nm and 281.3-404.2 nm, respectively, through transmission electron microscope analysis. The experimental results revealed that the color of the film significantly changes with variations in the CNC suspension concentration. Notably, the formation of the iridescent film is dependent on the concentration of CNC, with concentrations between 1.2% and 2.9% being optimal, and the aspect ratio of the CNC nanoparticles being around 11.3. X-ray diffraction analysis confirmed that the CNC nanoparticles possess the same crystal structure as microcrystalline cellulose (cellulose I). Fourier transform infrared spectroscopy revealed that the C[double bond, length as m-dash]C bond present in the liquid UV-curable coating disappeared upon UV irradiation. The performance of the CNC iridescent film, with varying thickness, was evaluated using UV-vis spectroscopy. The thermogravimetric analysis results indicate that the addition of CNC enhances the membrane's thermal stability and heat resistance. The results indicate that as the thickness of the CNC iridescent film increases, the corresponding UV-vis spectra display a redshift. The UV-WA/CNC shows potential in the field of decoration and establishing a straightforward, cost-effective, and efficient method for producing photonic materials with structural colors.

PARP-1 inhibits DNMT1-mediated promoter methylation and promotes linc01132 expression in benzene-exposed workers and hydroquinone-induced malignant transformed cells.

Hydroquinone (HQ), one of the main active metabolites of benzene, can induce the abnormal expression of long non-coding RNA (lncRNA). Studies have shown that lncRNA plays an important role in the occurrence of hematologic tumors induced by benzene or HQ. However, the molecular mechanism remains to be elucidated. Here, we investigated the molecular mechanism by which poly(ADP-ribose)polymerase 1 (PARP-1) interacts with DNA methyltransferase 1 (DNMT1) to regulate promoter methylation mediated linc01132 expression in HQ-induced TK6 malignant transformed cells (HQ-MT). The results revealed that the expression of linc01132 was increased in benzene-exposed workers and HQ-MT cells. The methylation of linc01132 promoter region was inhibited. Furthermore, in HQ-MT cells treated with 5-Aza-2'-deoxycytidine (5-AzaC) (DNA methyltransferase inhibitor) or trichostatin A (TSA) (histone deacetylation inhibitor), the expression of linc01132 was increased due to the regulation of DNA promoter methylation level by inhibiting DNMT1 expression. The methylation level of linc01132 promoter was correlated negatively with the expression of linc01132 in benzene-exposed workers, indicating that DNA methylation may contribute the expression of linc01132. Knockout of DNMT1, not DNMT3b, increased the expression of linc01132 as well as the demethylation of linc01132 promoter in HQ-MT cells. It was found that by knockdown PARP-1, the expression of DNMT1 in the nucleus was increased by immunofluorescence confocal microscopy, leading to the inhibition of hypermethylation in the promoter region of linc01132. Therefore, PARP-1 inhibits DNA methyltransferase (DNMT)-mediated promoter methylation and plays a role in linc01132 expression in benzene-exposed workers or HQ-MT cells, and is associated with benzene or HQ induced leukemia progression.

Gastric emptying performance of stomach-partitioning gastrojejunostomy versus conventional gastrojejunostomy for treating gastric outlet obstruction: A retrospective clinical and numerical simulation study.

Purpose: This study evaluated the gastric emptying performance of stomach-partitioning gastrojejunostomy (SPGJ) versus conventional gastrojejunostomy (CGJ) for treating gastric outlet obstruction (GOO). Methods: First, 73 patients who underwent SPGJ (n = 48) or CGJ (n = 25) were involved. Surgical outcomes, postoperative recovery of gastrointestinal function, delayed gastric emptying, and nutritional status of both groups were compared. Second, a three-dimensional stomach model was constructed based on the gastric filling CT images from a GOO patient with a standard stature. The present study evaluated SPGJ numerically by comparing it with CGJ in terms of local flow parameters such as flow velocity, pressure, particle retention time, and particle retention velocity. Results: Clinical data found that SPGJ had significant advantages over CGJ in terms of time to pass gas (3 versus 4 days, p < 0.001), time to oral intake (3 versus 4 days, p = 0.001), postoperative hospitalization (7 versus 9 days, p < 0.001), the incidence of delay gastric emptying (DGE) (2.1% versus 36%, p < 0.001), DGE grading (p < 0.001), and complications (p < 0.001) for GOO patients. Moreover, numerical simulation revealed that the SPGJ model would induce contents in stomach discharge to the anastomosis at a higher speed, and only 5% of that flowed to the pylorus. SPGJ model also had a low-pressure drop as the flow from the lower esophagus to the jejunum, reducing the resistance to food discharge. Besides, the average retention time of particles in the CGJ model is 1.5 times longer than that in the SPGJ models, and the average instantaneous velocity in CGJ and SPGJ models are 22 mm/s and 29 mm/s, respectively. Conclusion: Compared with CGJ, patients after SPGJ had better gastric emptying performance and better postoperative clinical efficacy. Therefore, we think that SPGJ may be a better option for treating GOO.

Safety and efficacy of laparoscopic proximal gastrectomy with SOFY versus laparoscopic total gastrectomy with Roux-en-Y for treating cT1-2 Siewert II/III adenocarcinoma of the esophagogastric junction: a single-center prospective cohort study.

PURPOSE: Side overlap with fundoplication by Yamashita (SOFY) is an anti-reflux form of esophagogastrostomy. We compared the safety and efficacy of laparoscopic proximal gastrectomy (PG) with SOFY to that of laparoscopic total gastrectomy (TG) with Roux-en-Y for treating cT1-2 Siewert II/III adenocarcinoma of the esophagogastric junction. METHODS: Fifty-two patients who underwent PG (n = 28) or TG (n = 24), without conversion to laparotomy, were included. Surgical outcomes, complications, reflux symptoms, quality of life, and nutritional status of both groups were compared. RESULTS: Significant differences between PG and TG groups regarding operative time (245.7 versus 294.6 min, P = 0.005), reconstruction time (22.1 versus 28.5 min, P < 0.001), time to pass gas (3 versus 4 days, P = 0.021), time to oral intake (4.5 versus 5 days, P = 0.043), and gastroesophageal reflux (60.7% versus 4.2%, P < 0.001) were observed. Reflux esophagitis for the PG group was 42.9% (12/28). The incidence of Los Angeles grade B and above was 10.7%. Between-group differences in terms of global health status, diarrhea, reflux, and eating were observed. Body weight maintenance was better in the PG group than in the TG group 6 months and 1 year postoperatively. CONCLUSION: SOFY is simple and more advantageous than TG in terms of postoperative recovery, body weight, eating, and diarrhea. However, the occurrence of postoperative reflux after SOFY was high. The limitations of this study are the significant differences in pathological T stage of patients in the two groups and the small sample size.

Hsa_circ_0001944 regulates apoptosis by regulating the binding of PARP1 and HuR in leukemia and malignant transformed cells induced by hydroquinone.

Hydroquinone (HQ) is one of the major metabolites of benzene and can cause abnormal gene expression. It is a known carcinogen that alters cell cycle disruption and cell proliferation. However, its chemical mechanism remain a mystery. Circular RNAs (circRNAs) are a subtype of noncoding RNAs (ncRNAs) that play a variety of roles in biological processes. Hsa_circ_001944 expression was upregulated in 30 leukemia patients and HQ-induced malignant transformed TK6 cells. Hsa_circ_001944 silencing inhibited the growth of HQ-TK6 cells and halted the cell cycle. The silencing of hsa_circ_0001944 led to increased cell accumulation in G1 versus S phase, increased apoptosis in the sh1944 versus the shNC group, and increased levels of DNA damage (γ-H2AX), leading to cell cycle arrest. In summary, inhibition of hsa_circ_001944 restricted cell growth by inhibiting cell cycle arrest and induced growth of HQ-TK6 cells by modulating PARP1 expression. Hsa_circ_0001944 targeted HuR, which is a kind of RNA-binding protein, to control PARP1 expression via RNAinter, RBPmap, and RBPdb. Fluorescence in situ hybridization combined with immunofluorescent labeling and western blotting experiments showed that hsa_circ_001944 was able to dissociate HuR and PARP1 binding in HQ-TK6 cells, control PARP1 production, and ultimately alter the PARP1/H-Ras pathway.

UV-curable self-matting waterborne polyurethane acrylate coating via self-wrinkled surface during curing in open-air.

This study developed and evaluated a series of ultraviolet (UV) curable self-matting waterborne polyurethane acrylate (UV-WPUA) coatings based on the self-wrinkled surface during UV-curing in the open-air. This method is simple, efficient, eco-friendly, and it does not require complicated or expensive equipment. The FT-IR spectrum indicates that the peaks of C[double bond, length as m-dash]C in UV-WPUA have disappeared after UV irradiation. The gloss value of the UV-WPUA cured film can be affected by the wrinkles on the surface of the film and adjusted it by controlling the content of the photoinitiator in the liquid coating, since the content influences the dimensions of the wrinkles. As the height of the wrinkle increased, the gloss value of the UV-WPUA cured film decreased, and when the incident angles are 20° and 60°, the gloss values are less than 3 GU and 5 GU, respectively. Moreover, the cured film has a maximum water contact angle of 109°, which is affected by wrinkles and positively correlated with the surface roughness of the film. Furthermore, the cured film has excellent properties of thermal stability, tensile strength, pencil hardness, cross-cut adhesion and resistance to abrasion properties, making it well suited for the furniture, leather, and textile applications.

KLF16 promotes pancreatic adenocarcinoma cell proliferation and migration by positively regulating SMAD6.

BACKGROUND: Pancreatic adenocarcinoma (PAAD) is a cancerous tumor with an extremely poor 5-year survival rate. The exploration of biomarkers for the diagnosis and treatment of PAAD is crucial in clinical practice. Krüppel-like factors (KLFs) are involved in a variety of biological functions in cells. According to multiple studies, KLF16 behave as an oncogene in prostate, breast and gastric cancers. However, no research has been done on the significance of KLF16 in PAAD. AIM: To explore the molecular mechanisms of KLF16 in PAAD. METHODS: KLF16 was identified in the tumor specimens and normal tissues by GEPIA database and verified by quantitative real-time PCR (qRT-PCR). Knockdown or exogenous expression of KLF16, combined with in vitro and in vivo assays, was performed to show the functional significance of KLF16. The molecular mechanism of KLF16 was demonstrated by qRT-PCR, western blotting, immunoprecipitation assay and flow cytometry. RESULTS: We showed that KLF16 was highly expressed in PAAD patients based on the GEPIA database. KLF16 silencing suppressed while KLF16 overexpression promoted the malignant function of PAAD cells. Based on RNA sequencing, we discovered that KLF16 potentiated the expression of SMAD6 in PAAD cells. SMAD6 transcript abundance was increased and positively correlated with KLF16 expression in PAAD samples. In addition, inhibiting SMAD6 was able to mitigate the effects of KLF16 overexpression on PAAD cell processes, suggesting the importance of SMAD6 in the development of KLF16-triggered PAAD. CONCLUSION: KLF16/SMAD6 axis might be explored as a therapeutic target for PAAD therapy.

Safety, efficacy, and selection strategy of laparoscopic local gastrectomy for gastrointestinal stromal tumors in the esophagogastric junction.

Objective: To investigate the safety, efficacy, and selection strategy of laparoscopic local gastrectomy for stromal tumors in the esophagogastric junction. Methods: Thirty-eight patients with mesenchymal tumors in the esophagogastric junction were retrospectively enrolled from April 2018 to July 2021 in which the upper edge of the tumor is less than 2 cm from the Z-line or has invaded the Z-line <1/2 circumference. Surgical outcomes, complications, recover, and postoperative gastroesophageal reflux of both groups were compared. Results: 27 patients underwent wedge resection, and 11 underwent resection by opening all of the layers of the stomach wall. Operative time (90.0 vs. 181.8 min, respectively, P = 0.001) was shorter for the WR group vs. RASW. Blood loss (20 vs. 50 ml, respectively, P = 0.012) was less for the WR group vs. RASW. Recovery of the RASW group was slower in terms of time to pass gas (2 vs. 3 days, P = 0.034), time to oral intake (2 vs. 4 days, P = 0.007), time to semi-liquid food intake (4 vs. 8 days, P = 0.003), and postoperative hospitalization (5 vs. 8 days, P = 0.001) vs. WR. In terms of short-term complications (≤30 days), no significant between-group differences were observed. Cardia stenosis did not occur in either group. In the WR group, one patient experienced mild reflux at 6 months and recovered 1 year after surgery. In the RASW group, one patient experienced severe gastroesophageal reflux at 6 months and 1 year after surgery, which was not entirely relieved by taking antacids. No other patients have gastroesophageal reflux. Conclusion: Laparoscopic local gastrectomy is safe and feasible for mesenchymal tumors in the esophagogastric junction in which the upper edge of the tumor is less than 2 cm from the Z-line or has invaded the Z-line <1/2 circumference, and has achieved an excellent short-term effect. The choice of surgery is based on the relationship between the tumor and the position of the cardia.

Exploring the scope of 4sb and 12a lymph node dissection for cT2-4 lower third gastric cancer: Study protocol for a prospective cohort trial.

Background: Currently, the extent of 4sb and 12a lymph node dissection is not clear and is based on the personal understanding of the surgeon. It may result in damage to the splenic artery and portal vein, leading to surgical complications. Therefore, this study aims to explore the scope of 4sb and 12a lymph node dissection in cT2-4 lower third gastric cancer. Methods: This is an ongoing prospective cohort trial. The total sample size required for the trial (March 2022 to February 2025) is approximately 524 patients. The participants are divided into the experimental (4sb first branch and 12a anterior lymphadenectomy) or control groups (traditional 4sb and 12a lymphadenectomy). Electronic data capture systems will be used to collect demographic, laboratory test, auxiliary examination, operation, postoperative condition, postoperative pathology, and follow-up data. The primary outcome is the 12a lymph node metastatic rate. Secondary outcomes include the pathology (consisting of the 4sb lymph node metastatic rate, the number of 4sb lymph nodes dissected, the number of 12a lymph nodes dissected and tumor pathological staging), a safety evaluation index (consisting of complications and mortality ≤30 days after surgery), an efficacy evaluation (consisting of operation data and postoperative recovery status), and follow-up data (consisting of 3-year or 5-year disease-free survival and overall survival). Discussion: By exploring the scope of 4sb and 12a lymph node dissection on the premise of ensuring radical cure of the tumor, the operation is simplified, the operation time is shortened, the damage of important blood vessels is reduced, the intraoperative and postoperative complications are reduced, and the patient recovers as soon as possible. Our study is a prospective exploration of the pathology, safety, efficacy, and prognosis of the new and traditional methods of 4sb and 12a lymph node dissection. Trial registration: Chinese Clinical Trial Registry, ChiCTR2200057698 (registration date: March 15, 2022).

PARP-1 modulates the expression of miR-223 through histone acetylation to involve in the hydroquinone-induced carcinogenesis of TK6 cells.

The upstream regulators of microRNAs were rarely reported. Hydroquinone (HQ) is the main metabolite of benzene, one of the important environmental factors contributing to leukemia and lymphoma. In HQ-induced malignant transformed TK6 (TK6-HT) cells, the expression of PARP-1 and miR-223 were upregulated. When in PARP-1 silencing TK6-HT cells, miR-223 was downregulated and the apoptotic cell number correspondingly increased. In TK6 cells treated with HQ for different terms, the expression of miR-223 and PARP-1 were dynamically observed and found to be decreased and increased, respectively. Trichostatin A could increase the expression of miR-223, then the expression of HDAC1-2 and nuclear factor kappa B were found to be increased, but that of mH2A was decreased. PARP-1 silencing inhibited the protein expression of H3Ac, mH2A, and H3K27ac. By co-immunoprecipitation experiment, PARP-1 and HDAC2 were found to form a regulatory complex. In conclusion, we demonstrated that the upregulation of PARP-1 mediated activation of acetylation to promote the transcription of miR-223 possibly via coregulating with HDAC2, an epigenetic regulation mechanism involved in cell malignant transformation resulting from long-term exposure to HQ, in which course, H3K27ac might be a specific marker for the activation of histone H3, which also gives hints for benzene exposure research.

Wood-cellulose photoluminescence material based on carbon quantum dot for light conversion.

To expand the application of transparent wood (TW) in the field of photoluminescence, lignin-based carbon quantum dots (CDs) were impregnated into wood cellulose template (CT) as a fluorescent functional material, the photoluminescent transparent wood (PTW) with light conversion was prepared. The results showed that FTW with different wavelength emissions could be obtained by controlling the CDs' conjugated size and surface functional groups. The loading of CDs does not affect the excellent transmittance (86.1%) and optical haze (73%) of TW. Compared to the original wood, the tensile properties of PTW have been enhanced from 368 MPa to 422 MPa. By controlling the content of different CDs, a PTW for white light conversion was prepared with the CIE color coordinates of (0.29, 0.34). This study is a new attempt to apply CDs to TW, providing a broad prospect for uniform light conversion and color display.

LINC00173 Interacts With DNMT1 to Regulate LINC00173 Expression via Promoter Methylation in Hydroquinone-Induced Malignantly Transformed TK6 Cells and Benzene-Exposed Workers.

Long-term exposure to benzene or its metabolite, hydroquinone (HQ), can causally contribute to acute myeloid leukemia. Long-noncoding RNAs are essential epigenetic regulators with critical roles in tumor initiation and malignant progression; however, the mechanism by which aberrantly expressed LINC00173 (long intergenic nonprotein coding RNA 173) regulates the pathogenesis of acute myeloid leukemia is not fully understood. Here, we found that the expression of LINC00173 decreased while the expression of DNA methyltransferase 1 (DNMT1) increased, and the methylation of LINC00173 promoter was negatively correlated with LINC00173 expression in GEPIA, CCLE databases, benzene-exposed workers, B-cell non-Hodgkin's lymphoma, K562, U937, or HQ-induced malignantly transformed TK6 (HQ-MT cells). Furthermore, in 5-aza-2'-deoxycytidine (DNA methyltransferase inhibitor) or trichostatin A (histone deacetylation inhibitor)-treated HQ-MT cells, the expression of LINC00173 was restored by reduced DNA promoter methylation levels. HQ-MT cells with DNMT1 knockout by CRISPR/Cas9 restored the expression of LINC00173 and inhibited the DNA methylation of its promoter as well as enrichment of DNMT1 to promoter. Overexpression of LINC00173 inhibited the expression of DNMT1, cell proliferation, tumor growth, enhanced chemosensitivity to cisplatin, and apoptosis in HQ-MT cells. LINC00173 interacts with DNMT1 to regulate the methylation of LINC00173 promoter. Overall, this study provides evidence that interaction between DNMT1 and LINC00173 regulates the expression of LINC00173 by regulating its promoter methylation level, thus regulating the function of HQ-MT cells in vitro and in vivo, providing a new therapeutic target for benzene-induced tumor.