Risk factors analyses associated with postoperative infection in choledochoscopy for intrahepatic bile duct stones (IHDs): a single-center retrospective study in real-world setting.

BACKGROUND: Choledochoscopy is a highly effective approach for managing intrahepatic bile duct stones (IHDs). However, postoperative infection is a common complication that significantly impacts treatment outcomes. Despite its clinical relevance, the risk factors associated with this procedure remain largely unexplored. METHODS: This study focused on a consecutive cohort of patients who underwent choledochoscopy for IHDs at our institution between January 2016 and December 2022. The primary objective was to analyze the relationship between various clinical factors and postoperative infection, and to compare the postoperative infection of different choledochoscopic procedures. RESULTS: The study cohort consisted of 126 patients, with 60 individuals (47.6%) experiencing postoperative infection. Notably, preoperative biliary obstruction (odds ratio [OR] 1.861; 95% confidence interval [CI] 1.314-8.699; p = 0.010) and operation time (OR 4.414; 95% CI 1.635-12.376; p = 0.004) were identified as risk factors for postoperative infection. Additionally, biliary tract infections (60.00%) were primarily responsible for postoperative infection, with Escherichia coli (47.22%) being the predominant bacterial strain identified in bile cultures. Furthermore, biliary tract obstruction (OR 4.563; 95% CI 1.554-13.401; p = 0.006) and body mass index (BMI) (OR 1.186; 95% CI 1.015-1.386; p = 0.031) were determined to be independent risk factors for postoperative biliary tract infection. CONCLUSIONS: The occurrence of postoperative infection in patients undergoing choledochoscopy was primarily associated with the duration of the operation and the presence of preoperative biliary obstruction.

Up-Front Versus Delayed Thermal Ablation for Colorectal Liver Oligometastases: A Multicenter Retrospective Study Using Propensity Score Matching.

BACKGROUND. Thermal ablation combined with systemic therapy is an accepted treatment of colorectal liver oligometastases (CLOM). Consensus is lacking regarding the optimal timing of thermal ablation relative to systemic therapy. OBJECTIVE. The purpose of our study was to compare delayed and up-front thermal ablation in terms of efficacy and safety in the treatment of patients with CLOM. METHODS. This retrospective multicenter study included 440 patients (316 men, 124 women; mean age, 57.1 ± 11.1 [SD] years) with CLOM from nine hospitals between October 2009 and December 2020. Patients underwent delayed (n = 322) or up-front (n = 118) thermal ablation in combination with systemic therapy. Analyses included all patients using crude data, all patients using inverse probability treatment weighting (IPTW), and a subset of patients using propensity score matching (PSM) at a 1:1 ratio to balance baseline variables (108 matched patients for each group [i.e., delayed ablation and up-front ablation]). Patients were classified as having a low or high tumor burden score (TBS) on the basis of the number and size of the liver metastases. The primary outcome was progression-free survival (PFS); secondary outcomes included overall survival (OS), complications from ablation, and adverse events (AEs) from systemic therapy. Survival analysis used the Kaplan-Meier method. RESULTS. The median follow-up was 2.9 years. The 5-year PFS was 17.1% for delayed ablation versus 33.6% for up-front ablation in all patients and 17.9% versus 34.7% after PSM. Delayed ablation was associated with worse PFS in the crude analysis (HR = 0.62), IPTW analysis (HR = 0.66), and PSM analysis (HR = 0.62) (all p < .05). No analysis showed a significant difference in OS between delayed and up-front ablation. Crude, IPTW, and PSM analyses showed better PFS for up-front compared with delayed ablation in patients with a low TBS (HR = 0.62-0.67; all p < .05); none of these analyses showed significant difference in PFS in patients with a high TBS. Delayed ablation and up-front ablation groups showed no difference in frequency of grade III or IV ablation complications (4.7% vs 6.8%, p = .38) or grade III or IV systemic therapy AEs (12.4% vs 10.2%, p = .53). CONCLUSION. In patients with CLOM, up-front ablation achieved better PFS compared with delayed ablation, although only among patients with a low TBS. CLINICAL IMPACT. These findings could help optimize clinical implementation of thermal ablation in patients who are not candidates for surgical resection.

Single layer aligned semiconducting single-walled carbon nanotube array with high linear density.

Highly ordered semiconducting single-walled carbon nanotubes(sc-SWCNTs) array with high purity, high linear density and controllable manner is strongly desired for carbon-based integrated circuits, yet it remains a big challenge. Herein, close-packed single layered and controllably aligned sc-SWCNTs arrays were obtained through dielectrophoresis using a high purity sc-SWCNT dispersion. Under optimized condition of length and average number of interconnecting junctions across the channel full of aligned sc-SWCNTs, field effect transistors (FETs) with high performance were achieved with both a high on/off current ratio and large carrier mobility. Based on the optimized channel length, by systematically optimizing the dielectrophoresis parameters of the frequency and duration of applied AC voltage (Vpp), the highly ordered sc-SWCNTs arrays with an ultra-high linear density of 54 ± 2 tubesµm-1showed relatively high device performance of FET. The fabrication process optimized in this report can be further extended and applied in large-area, low-cost carbon-based integrated circuits.

Experimental and Modeling Studies on the Filtration of SiO2 Nanoparticles Aerosolized from Different Solvents.

The filtration performance of a fibrous filter in removing nano-SiO2 aerosols atomized using different solvents including methanol, ethanol, 1-propanol, water, and the ethanol/water mixture has been investigated. Through discrete element method (DEM) simulation and filtration experiments, the efficiency variation caused by the combinative interaction of the particle-filter adhesion and interparticle attraction has been analyzed and verified. The adhesion force between the solvent-coated nanoparticles and the filter is considered as the key factor to influence their initial filtration efficiency and can be balanced by their interparticle interaction. The stronger the adhesion, the higher the initial filtration efficiency. Primary aggregate is formed through the particle-fiber interaction, and further agglomerate is caused by particle migration on the fibers, i.e. secondary aggregate. Hydrogen bonding interaction is considered as the main factor causing interparticle secondary agglomeration, and plenty of OH groups existing in the nano-SiO2 aerosols yielded from alcohol promotes the particle secondary aggregation. As a result, the Brown diffusion capture of the filter is significantly abated, and the as-formed agglomerate is scraped off the filter surface by the alcohol molecules, causing the filtration efficiency decreases. This study highlights the surface affinity properties of nanoaerosols and their balance between particle-particle and particle-fiber interactions in the filtration process.

A Simple Fluorescence Quenching Method for the Determination of Vanillin Using TGA-capped CdTe/ZnS Nanoparticles as Probes.

Based on the quenching of the fluorescence intensity of thioglycolic acid (TGA)-capped core-shell CdTe/ZnS nanoparticles (NPs) by vanillin, a novel, simple and rapid method for the determination of vanillin was proposed. In aqueous medium, the functionalized core-shell CdTe/ZnS NPs were successfully synthesized with TGA as the capping ligand. TGA-capped core-shell CdTe/ZnS NPs were characterized by using X-ray diffraction (XRD), transmission electron microscopy (TEM) and Fourier transform infrared (FTIR) spectroscopy. Factors affecting the vanillin detection were investigated, and the optimum conditions were also determined. Under the optimum conditions, the relative fluorescence intensity of CdTe/ZnS NPs was linearly proportional to vanillin over a concentration range from 9.4 × 10(-7) to 5.2 × 10(-4) M with a correlation coefficient of 0.998 and a detection limit of 2.6 × 10(-7) M. The proposed method was also employed to detect trace vanillin in cookies with satisfactory results.

High-throughput sequencing of natively paired antibody chains provides evidence for original antigenic sin shaping the antibody response to influenza vaccination.

We developed a DNA barcoding method to enable high-throughput sequencing of the cognate heavy- and light-chain pairs of the antibodies expressed by individual B cells. We used this approach to elucidate the plasmablast antibody response to influenza vaccination. We show that >75% of the rationally selected plasmablast antibodies bind and neutralize influenza, and that antibodies from clonal families, defined by sharing both heavy-chain VJ and light-chain VJ sequence usage, do so most effectively. Vaccine-induced heavy-chain VJ regions contained on average >20 nucleotide mutations as compared to their predicted germline gene sequences, and some vaccine-induced antibodies exhibited higher binding affinities for hemagglutinins derived from prior years' seasonal influenza as compared to their affinities for the immunization strains. Our results show that influenza vaccination induces the recall of memory B cells that express antibodies that previously underwent affinity maturation against prior years' seasonal influenza, suggesting that 'original antigenic sin' shapes the antibody response to influenza vaccination.

Identifying functional anti-Staphylococcus aureus antibodies by sequencing antibody repertoires of patient plasmablasts.

Infection by Staphylococcus aureus is on the rise, and there is a need for a better understanding of host immune responses that combat S. aureus. Here we use DNA barcoding to enable deep sequencing of the paired heavy- and light-chain immunoglobulin genes expressed by individual plasmablasts derived from S. aureus-infected humans. Bioinformatic analysis of the antibody repertoires revealed clonal families of heavy-chain sequences and enabled rational selection of antibodies for recombinant expression. Of the ten recombinant antibodies produced, seven bound to S. aureus, of which four promoted opsonophagocytosis of S. aureus. Five of the antibodies bound to known S. aureus cell-surface antigens, including fibronectin-binding protein A. Fibronectin-binding protein A-specific antibodies were isolated from two independent S. aureus-infected patients and mediated neutrophil killing of S. aureus in in vitro assays. Thus, our DNA barcoding approach enabled efficient identification of antibodies involved in protective host antibody responses against S. aureus.

Meta-analysis of the association of glutathione S-transferase T1 null/presence gene polymorphism with the risk of gastric carcinoma.

A possible association of glutathione S-transferase T1 (GSTT1) null/presence gene polymorphism and an increased risk of developing gastric carcinoma is still unclear and hotly debated. This investigation was performed to assess the association of the GSTT1 null/presence gene polymorphism with the risk of gastric carcinoma via a meta-analysis to increase sample size and statistical significance. PubMed, Cochrane Library and CBM-disc (China Biological Medicine Database) were searched on March 1, 2013, association reports were identified, and eligible studies were recruited and synthesized. Fifty-two reports were found to be suitable for this meta-analysis for the association of the GSTT1 null genotype with gastric carcinoma risk. The results showed that there was a significantly increased gastric carcinoma risk when the GSTT1 null genotype was present in the overall population (OR 1.21, 95 % CI 1.11-1.32, P < 0.0001), Caucasians (OR 1.25, 95 % CI 1.05-1.48, P = 0.01), East-Asians (OR 1.18, 95 % CI 1.06-1.31, P = 0.003), and Chinese (OR 1.24, 95 % CI 1.07-1.44, P = 0.005). However, no statistically relevant association could be established for the Indian ethnic group (OR 1.33, 95 % CI 0.94-1.90, P = 0.11). In conclusion, the GSTT1 null genotype is associated with an increased gastric carcinoma risk in the overall population, Caucasians, East-Asians, and Chinese.

Total endoscopic thyroidectomy via bilateral breast and ipsilateral axillary approach: a clinical feasibility study.

The most commonly used minimally invasive thyroid surgery via noncervical approach is the bilateral breast approach, but there was usually a scar in the chest wall, which induced uncomfortable and bad cosmetic result. For this reason, endoscopic thyroidectomy via bilateral breast and ipsilateral axillary approach had been developed. The aims of this study are to analyze our surgical outcomes and to evaluate the effectiveness and safety. Between May 2011 and August 2012, 64 patients with thyroid diseases underwent endoscopic thyroidectomy via bilateral breast and ipsilateral axillary approach. The patients' clinical data, operative time, blood loss, drainage amounts, complications, hospital stay, area of skin flap, and postoperative visual analog pain score (VAS) were analyzed retrospectively. We describe here the details of our operative technique. All the 64 patients successfully underwent endoscopic thyroidectomy. None had to be converted, and no postoperative complications were observed. Mean operation time was 104.0 ± 25.3 minutes. Mean blood loss was 10.5 ± 3.7 mL. Mean average area of skin flap was 78.6 ± 8.6 cm2. Mean postoperative drainage amounts on day 1 were 84.5 ± 62.6 mL. Mean hospital stay was 2 to 3 days. The postoperative VAS scores on day 1 were 0 to 2. Follow-up visits range from 2 to 12 months, suggesting that no one had a relapse. Furthermore, the patients were uniformly pleased with the cosmetic results of the operation. Bilateral breast and ipsilateral axillary approach is a safe and easily popularized method that gives good surgical completeness, quick recovery, less pain, less postoperative complications, and an excellent cosmetic result. Therefore, this method is a good choice for patients with surgical thyroid diseases.

Pan-cancer analysis reveals PDK family as potential indicators related to prognosis and immune infiltration.

Pyruvate dehydrogenase kinases (PDKs) play a key role in glucose metabolism by exerting negative regulation over pyruvate dehyrogenase complex (PDC) activity through phosphorylation. Inhibition of PDKs holds the potential to enhance PDC activity, prompting cells to adopt a more aerobic metabolic profile. Consequently, PDKs emerge as promising targets for condition rooted in metabolic dysregulation, including malignance and diabetes. However, a comprehensive exploration of the distinct contribution of various PDK family members, particularly PDK3, across diverse tumor types remain incomplete. This study undertakes a systematic investigation of PDK family expression patterns, forging association with clinical parameters, using data from the TCGA and GTEx datasets. Survival analysis of PDKs is executed through both Kaplan-Meier analysis and COX regression analysis. Furthermore, the extent of immune infiltration is assessed by leveraging the CIBERSORT algorithm. Our study uncovers pronounced genetic heterogeneity among PDK family members, coupled with discernible clinical characteristic. Significantly, the study establishes the potential utility of PDK family genes as prognostic indicators and as predictors of therapeutic response. Additionally, our study sheds light on the immune infiltration profile of PDK family. The results showed the intimate involvement of these genes in immune-related metrics, including immune scoring, immune subtypes, tumor-infiltrating lymphocytes, and immune checkpoints expression. In sum, the findings of this study offer insightful strategies to guide the therapeutic direction, aiming at leveraging the impact of PDK family genes in cancer treatment.

Bulk and single-cell RNA sequencing analysis with 101 machine learning combinations reveal neutrophil extracellular trap involvement in hepatic ischemia-reperfusion injury and early allograft dysfunction.

BACKGROUND: Hepatic ischaemia-reperfusion injury (HIRI) is a major clinical concern during the perioperative period and is closely associated with early allograft dysfunction (EAD), acute rejection (AR) and long-term graft survival. Neutrophil extracellular traps (NETs) are extracellular structures formed by the release of decondensed chromatin and granular proteins following neutrophil stimulation. There is growing evidence that NETs are involved in the progression of various liver transplantation complications, including ischaemia-reperfusion injury (IRI). This study aimed to comprehensively analyse the expression patterns of NET-related genes (NRGs) in HIRI, identify HIRI subtypes with distinct characteristics, and develop a reliable EAD prediction model. METHODS: Microarray, bulk RNA-seq, and single-cell sequencing datasets were obtained from the GEO database. Initially, differentially expressed NRGs (DE-NRGs) were identified using differential gene expression analyses. We then utilised a non-negative matrix factorisation (NMF) algorithm to classify HIRI samples. Subsequently, we employed machine learning algorithms to screen the hub NRGs related to EAD and developed an EAD prediction model based on these hub NRGs. Concurrently, we assessed the expression patterns of hub NRGs at the single-cell level using the HIRI. Additionally, we validated C5AR1 expression and its effect on HIRI and NETs formation in a rat orthotopic liver transplantation (OLT) model. RESULTS: In this study, we identified 11 DE-NRGs in the HIRI context. Based on these 11 DE-NRGs, HIRI samples were classified into two distinct clusters. Cluster1 exhibited a low expression of DE-NRGs, minimal neutrophil infiltration, mild inflammation, and a low incidence of EAD. Conversely, Cluster2 displayed the opposite phenotype, with an activated inflammatory subtype and a higher incidence of EAD. Furthermore, an EAD prediction model was developed using the four hub NRGs associated with EAD. Based on risk scores, HIRI samples were classified into high- and low-risk groups. The OLT model confirmed substantial upregulation of C5AR1 expression in the liver tissue, accompanied by increased formation of NETs. Treatment with a C5AR1 antagonist improved liver function, reduced tissue inflammation, and decreased NETs formation. CONCLUSIONS: This study distinguished two apparent HIRI subtypes, established a predictive model for EAD, and validated the effect of C5AR1 on HIRI. These findings provide novel perspectives for the development of advanced clinical strategies to enhance the outcomes of liver transplant recipients.

The integration of bulk and single-cell sequencing data revealed the function of FKBP10 in the gastric cancer microenvironment.

Background: Due to the implementation of individualized treatment, the majority of gastric cancer patients have a favorable prognosis, but advanced gastric cancer with recurrence and distant metastasis still plagues some patients. As a member of the FK506-binding protein (FKBP65) family, there is growing evidence that FKBP10 plays a crucial role in tumorigenesis. However, the role of FKBP10 in the tumor microenvironment (TME) has been a prominent issue. Methods: The FKBP10 knockdown efficiency in gastric cancer cells was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Wound healing and transwell analysis were performed to detect variations in cell invasion and migration. We integrated single-cell and bulk sequencing data to further elaborate the impact of FKBP10 and FKBP10-coexpressed genes (FCGs) in the TME via a variety of bioinformatics approaches. Results: Here, we found that FKBP10 knockdown inhibited cell invasion and metastasis. FKBP10 was chiefly expressed in inflammatory cancer-associated fibroblasts (iCAFs), and FCGs principally mediated alterations in extracellular matrix (ECM) organization. Besides, according to nine prognosis-related FCGs, two disparate clusters were identified, and differences in tumor immune infiltration characteristics and immunotherapy response between different clusters were investigated. Conclusions: Our study provides insights into the expression and function of FKBP10 in the microenvironment of gastric cancer.

Anisotropic mechanical properties of α-MoO3 nanosheets.

The mechanical behaviors of 2D materials are fundamentally important for their potential applications in various fields. α-Molybdenum trioxide (α-MoO3) crystals with unique electronic, optical, and electrochemical properties, have attracted extensive attention for their use in optoelectronic and energy conversion devices. From a mechanical viewpoint, however, there is limited information available on the mechanical properties of α-MoO3. Here, we developed a capillary force-assisted peeling method to directly transfer α-MoO3 nanosheets onto arbitrary substrates. Comparatively, we could effectively avoid surface contamination arising from the polymer-assisted transfer method. Furthermore, with the help of an in situ push-to-pull (PTP) device during SEM, we systematically investigated the tensile properties of α-MoO3. The measured Young's modulus and fracture strengths along the c-axis (91.7 ± 13.7 GPa and 2.1 ± 0.9 GPa, respectively) are much higher than those along the a-axis (55.9 ± 8.6 GPa and 0.8 ± 0.3 GPa, respectively). The in-plane mechanical anisotropy ratio can reach ∼1.64. Both Young's modulus and the fracture strength of MoO3 show apparent size dependence. Additionally, the multilayer α-MoO3 nanosheets exhibited brittle fracture with interplanar sliding due to poor van der Waals interaction. Our study provides some key points regarding the mechanical properties and fracture behavior of layered α-MoO3 nanosheets.

MICA+ Tumor Cell Upregulated Macrophage-Secreted MMP9 via PROS1-AXL Axis to Induce Tumor Immune Escape in Advanced Hepatocellular Carcinoma (HCC).

BACKGROUND: tumor-associated macrophages (TAMs) constitute a significant proportion of non-cancerous cells within the intricate tumor microenvironment (TME) of hepatocellular carcinoma (HCC). Understanding the communication between macrophages and tumor cells, as well as investigating potential signaling pathways, holds promise for enhancing therapeutic responses in HCC. METHODS: single-cell RNA-sequencing data and bulk RNA-sequencing data were derived from open source databases Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Through this analysis, we elucidated the interactions between MICA+ tumor cells and MMP9+ macrophages, primarily mediated via the PROS1-AXL axis in advanced HCC. Subsequently, we employed a range of experimental techniques including lentivirus infection, recombinant protein stimulation, and AXL inhibition experiments to validate these interactions and unravel the underlying mechanisms. RESULTS: we presented a single-cell atlas of advanced HCC, highlighting the expression patterns of MICA and MMP9 in tumor cells and macrophages, respectively. Activation of the interferon gamma (IFN-γ) signaling pathway was observed in MICA+ tumor cells and MMP9+ macrophages. We identified the existence of an interaction between MICA+ tumor cells and MMP9+ macrophages mediated via the PROS1-AXL axis. Additionally, we found MMP9+ macrophages had a positive correlation with M2-like macrophages. Subsequently, experiments validated that DNA damage not only induced MICA expression in tumor cells via IRF1, but also upregulated PROS1 levels in HCC cells, stimulating macrophages to secrete MMP9. Consequently, MMP9 led to the proteolysis of MICA. CONCLUSION: MICA+ HCC cells secreted PROS1, which upregulated MMP9 expression in macrophages through AXL receptors. The increased MMP9 activity resulted in the proteolytic shedding of MICA, leading to the release of soluble MICA (sMICA) and the subsequent facilitation of tumor immune escape.

Prediction model of clinical prognosis and immunotherapy efficacy of gastric cancer based on level of expression of cuproptosis-related genes.

Background: Gastric cancer is one of the most common malignancies in the world and ranks fourth among cancer-related causes of death. Gastric adenocarcinoma is the most common pathological type of gastric cancer; usually, this tumor is associated with distant metastasis upon first diagnosis and has a poor prognosis. Cuproptosis is a novel mechanism of cell death induced by copper, and is closely related to tumor progression, prognosis and immune response. However, the role of cuproptosis-related genes (CRGs) in the tumor microenvironment (TME) of gastric cancer has yet to be elucidated. Methods: Gastric adenocarcinoma data were downloaded from the Cancer Genome Atlas (TCGA) database. Through bioinformatics analysis, a risk scoring model was constructed from cuproptosis gene-related lncRNA. Then, we investigated the relationship between prognosis and the TIME of gastric cancer according to clinical characteristics and risk score. Results: Validation of the model showed that the overall survival (OS) of the high-risk group was significantly lower than that of the low-risk group (P < 0.001) and that the risk score was an independent predictor of prognosis (P < 0.001). The new model was significantly correlated with the prognosis and TIME of patients with gastric cancer, including immune cell infiltration, tumor mutation burden (TMB) score, targeted drug sensitivity, and immune checkpoint gene expression. In addition, a prognostic nomogram was established based on the risk score (AC008915.2, AC011005.4, AC023511.1, AC139792.1, AL355312.2, LINC01094 and LINC02476). Conclusion: Our analysis revealed that the prognostic model of cuproptosis-related genes could effectively predict the prognosis of patients with gastric cancer and comprehensively establish the relationship between cuproptosis genes and tumor immunity. This may provide a new strategy for the precise treatment of gastric cancer.

Comprehensive analysis to long non-coding RNA-mediated high expression of GNG5 correlates with better prognosis and tumor immune infiltration of colon carcinoma.

BACKGROUND: Colorectal cancer is the third most common cancer and the fourth leading cause of cancer deaths. Prognosis is poor. The majority of patients are diagnosed with locally advanced or metastatic disease. Increasing evidence suggests G protein subunit gamma 5 (GNG5) play key roles in several types of human cancer. The key gating mechanisms in colorectal cancer remains unkown. METHODS: In this study, pan-cancer analyses have been performed for GNG5's expression. Prognosis using The Cancer Genome Atlas and The Genotype-Tissue Expression data found that GNG5 are activated oncogenes in colorectal cancer. Noncoding RNAs play increasingly appreciated gene-regulatory roles and long noncoding RNAs contributing to GNG5 overexpression. They were identified by a combination in silico computational analyses. We identified candidate regulators controlling colon carcinoma survival analysis and correlation analysis. RESULTS: The SNHG4/DRAIC-let-7c-5p axis was identified as the most progressive upstream lncRNA-related pathway of GNG5 in colorectal cancer. The GNG5 level was significantly negatively correlated with tumor immune cell infiltration, immune cell biomarkers, and immune checkpoint expression. CONCLUSIONS: Our findings elucidated that lncRNAs-mediated downregulation of GNG5 correlated with better prognosis and tumor immune infiltration in colorectal cancer.

Delimiting Low Level of Difficulty Scoring System Based on the Extent of Resection Difficulty Scoring System for Laparoscopic Liver Resection.

Background: The difficulty scoring system based on the extent of resection (DSS-ER) is a common tool for assessing the difficulty and risk of laparoscopic liver resection (LLR), but DSS-ER fails to comprehensively and accurately assess low level for beginners. Methods: The 93 cases of LLRs for primary liver cancer in the general surgery department of the Second Affiliated Hospital of Guangxi Medical University from 2017 to 2021 were retrospectively analyzed. The low level of DSS-ER difficulty scoring system was reclassified into three grades. The intraoperative and postoperative complications were compared among different groups. Results: There were significant differences in the operative time, blood loss, intraoperative allogeneic blood transfusion, conversion to laparotomy, and allogeneic blood transfusion among the different groups. Meanwhile, the postoperative complications were mainly pleural effusion and pneumonia, and the incidence of grade III was higher compared with other two grades. No significant difference existed in the postoperative biliary leakage and liver failure among three grades. Conclusions: This reclassified low level of DSS-ER difficulty scoring system has certain clinical value for LLR beginners to complete the corresponding learning curve.

Inhibition of Checkpoint Kinase 1 (CHK1) Upregulates Interferon Regulatory Factor 1 (IRF1) to Promote Apoptosis and Activate Anti-Tumor Immunity via MICA in Hepatocellular Carcinoma (HCC).

BACKGROUND: CHK1 is considered a key cell cycle checkpoint kinase in DNA damage response (DDR) pathway to communicate with several signaling pathways involved in the tumor microenvironment (TME) in numerous cancers. However, the mechanism of CHK1 signaling regulating TME in hepatocellular carcinoma (HCC) remains unclear. METHODS: CHK1 expression in HCC tissue was determined by IHC staining assay. DNA damage and apoptosis in HCC cells induced by cisplatin or CHK1 inhibition were detected by WB and flow cytometry. The interaction of CHK1 and IRF1 was analyzed by single-cell RNA-sequence, WB, and immunoprecipitation assay. The mechanism of IRF1 regulating MICA was investigated by ChIP-qPCR. RESULTS: CHK1 expression is upregulated in human HCC tumors compared to the background liver. High CHK1 mRNA level predicts advanced tumor stage and worse prognosis. Cisplatin and CHK1 inhibition augment cellular DNA damage and apoptosis. Overexpressed CHK1 suppresses IRF1 expression through proteolysis. Furthermore, single-cell RNA-sequence analyses confirmed that MICA expression positively correlated with IRF1 in HCC cells. Immunoprecipitation assay showed the binding between CHK1 and IRF1. Cisplatin and CHK1 inhibition upregulate MICA expression through IRF1-mediated transcriptional effects. A novel specific cis-acting IRF response element was identified at -1756 bp in the MICA promoter region that bound IRF1 to induce MICA gene transcription. MICA may increase NK cell and CD8+T cell infiltration in HCC. CONCLUSIONS: DNA damage regulates the interaction of CHK1 and IRF1 to activate anti-tumor immunity via the IRF1-MICA pathway in HCC.

Risk Factors and Long-Term Implications of Unplanned Conversion During Laparoscopic Liver Resection for Hepatocellular Carcinoma.

Background: Laparoscopic liver resection (LLR) has become a widely used standardized operation for patients with hepatocellular carcinoma (HCC) in the field of hepatic surgery. However, the risk factors and long-term implications associated with unplanned conversion to an open procedure during the LLR have not been adequately studied. Methods: The study incorporated 96 patients with HCC. Risk factors of conversion and their prognosis were analyzed by comparing patients who successfully underwent LLR with those who required unplanned conversion. Results: In this study, the unplanned conversion rate for laparoscopic hepatectomy was 42.7%. Patients who underwent conversion had longer length of stay (8 versus 7 days, P < .001), longer operation time (297.73 versus 194.03 minutes, P = .000), a higher transfusion rate (29.3% versus 5.5%, P < .001), and more postoperative complications compared with patients who successfully underwent LLR. The two surgical maneuvers did not show substantial disparities in terms of total survival and disease-free survival rates. Risk factors of unplanned conversion contained tumor location (odds ratio [OR], 3.129; 95% confidence interval [CI]: 1.214-8.066; P = 0.018) and tumor size (OR, 2.652; 95% CI: 1.039-6.767; P = 0.041). Conclusions: The unplanned conversion during LLR for HCC was linked to unfavorable short-term prognosis, yet it did not influence long-term oncologic outcomes. Moreover, preoperative evaluation of tumor size and location may effectively reduce the probability of unplanned conversion during LLR.

Green tea extracts alleviate acetic acid-induced oral inflammation and reconstruct oral microbial balance in mice.

Oral cavity contains the second largest microbial community in the human body. Due to the highly vascularized feature of mouth, oral microbes could directly access the bloodstream and affect the host healthy systemically. The imbalance of oral microbiota is closely related to various oral and systemic diseases. Green tea extracts (GTE) mainly contain tea polyphenols, alkaloids, amino acid, flavones, and so on, which equipped with excellent anti-inflammatory activities. Previous studies have demonstrated the beneficial effects of GTE on oral health. However, most researches used in vitro models or focused on limited microorganisms. In this study, the regulatory effect of GTE on oral microbiome and the alleviative effect on oral inflammation in vivo were evaluated. The results showed that GTE could efficiently alleviate the inflammations of the tongue, cheek pouch, as well as throat. GTE effectively inhibited the activation of NF-κB through the upregulation of the anti-inflammatory cytokine interleukin (IL)-10, consequently leading to reduced expression of pro-inflammatory cytokines IL-6 and tumor necrosis factor-α. The indexes of spleen and thymus were also elevated by GTE in stomatitis mice. Moreover, GTE promoted the growth of probiotics Lactobacillus and Bacillus, inhibited the reproduction of pathogens Achromobacter, reversing the microbiota disorders in oral cavity. This study not only presents a novel approach for enhancing oral microecology but also facilitates the wider adoption of tea consumption.