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BackgroundHepatocellular carcinoma (HCC) is a common malignant tumor of the digestive system with a high incidence that seriously threatens patients’ lives and health. However, with the rise and application of new treatments, such as immunotherapy, there are still some restrictions in the treatment and diagnosis of HCC, and the therapeutic effects on patients are not ideal.MethodsTwo single-cell RNA sequencing (scRNA-seq) datasets from HCC patients, encompassing 25,189 cells, were analyzed in the study. We utilized non-negative matrix factorization (NMF) clustering to identify mitophagy patterns in HCC TME cells, including cancer-associated fibroblasts (CAFs), T cells, B cells, and tumor-associated macrophages (TAMs). Cell-to-cell communication was analyzed using the CellChat package, and pseudotime trajectory analysis was performed using the Monocle package. Gene regulatory networks were investigated with the SCENIC package, and survival analyses were conducted with mitophagy-related signatures.ResultsHCC samples analysis identified 22 clusters, including 7 principal cell types. Complex cell communications were observed among these cell types. Mitophagy-related CAFs, TAMs, CD8+ T cells, and B cells were identified. These subtypes had different biological states, cell-cell communications, and metabolic pathways. Mitophagy levels were elevated in tumor samples. Changes in mitophagy-related genes within specific cell subtypes were associated with different overall survival rates. However, mitophagy did not seem to affect the effectiveness of immunotherapy.ConclusionThis study provides evidence that mitophagy within the HCC TME modulates intercellular communication, influencing tumor progression and patient prognosis. Targeting mitophagy may offer a promising approach to improve the long-term prognosis of HCC patients.

In the suspension cage culture process, regular cleaning to remove epiphytic organisms from the cage is essential to prevent economic losses due to the sinking of the cage. However, after cleaning, many of attachments from the suspension cage accumulate in the tidal flats, causing environmental pollution and resource wastage. Moreover, because sea cucumbers (Apostichopus japonicus) are sedimentary food organisms, sea mud is typically added to their feed to varying degrees. However, long-term excavation of sea mud can destroy the marine environment. Therefore, developing an alternative new raw feed material to replace sea mud in sea cucumber feed is necessary to promote sustainable development of the A. japonicus aquaculture industry. The aim of this study was to explore the feasibility of using fermented attachments of suspension cage (FASC) as a raw feed material for A. japonicus. Different FASC concentrations (0, 25, 50, 75, and 100 %) were used in A. japonicus feed for 60 d. Replacing Sea mud with 100 % FASC significantly improved sea cucumber growth, reduced the feed coefficient, significantly increased the activity of intestinal digestive enzymes, improved intestinal structure, and enriched intestinal microbiome diversity. Furthermore, expressions of growth genes mapk-7 and fgfr-1 significantly increased in the 100 % FASC treatment compared with that in the control, and that of negative growth regulator gene gdf-8 was inhibited. The results suggested the potential of FASC as a new raw feed material for A. japonicus.

Background/Aims: In this study, we evaluated the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with hepatic arterial infusion chemotherapy (HAIC) compared to TACE monotherapy for the treatment of unresectable hepatocellular carcinoma (HCC). Materials and Methods: Relevant studies were systematically searched in PubMed, Embase, Web of Science, and Cochrane Library databases until September 1, 2023. Our analysis included 7 cohort studies encompassing a total of 630 patients. Results: The results demonstrated that the TACE plus HAIC group exhibited significantly improved prognosis compared to the TACE alone group, as evidenced by superior rates of complete response, partial response, progressive disease, objective response rate, and disease control rate. Moreover, the TACE group displayed a lower risk of platelet reduction and vomiting when compared to the TACE plus HAIC group. None of the 7 studies reported any intervention-related mortality. Conclusion: In conclusion, the combination of TACE and HAIC may be recommended as a viable option for patients with unresectable HCC, given its evident enhancements in survival and tumor response rates without significant differences in adverse events when compared to TACE monotherapy. Nevertheless, additional randomized controlled trials and studies involving Western cohorts are warranted to further validate these findings.

Abstract Background The currently preferred minimally invasive approaches have substantially improved outcomes of infected walled-off pancreatic necrosis (iWON). However, iWON with deep extension (iWONde) still poses a tricky challenge for sufficient necrosis evacuation by one stand-alone approach, often requiring repeated interventions. The aim of this study was to assess the effectiveness and safety of a minimal-access video-assisted retroperitoneal and/or transperitoneal debridement (hereafter called VARTD) in the management of iWONde. Methods Patients who had developed an iWONde were recruited to receive the VARTD in this prospective single-arm study. The primary efficacy endpoint was clinical improvement up to day 28 after the VARTD, defined as a ≥ 75% reduction in size of necrotic collection (in any axis) on CT and clinical resolution of sepsis or organ dysfunction. The primary safety endpoint was a composite of major complications or death during follow-up. Six-month postdischarge follow-up was available. Results Between July 18, 2018, and November 12, 2020, we screened 95 patients with necrotizing pancreatitis; of these, 21 iWONde patients (mean [SD] age, 42.9 [11.7] years; 10 [48%] women) were finally enrolled. The primary efficacy endpoint was achieved by most participants (14/21, 67%). No participants required repeated interventions. The primary safety endpoint occurred in six patients (29%). Except one in-hospital death attributable to repeated intra-abdominal hemorrhage, others were discharged without any major complication. Conclusions The VARTD approach appears to have a reasonable efficacy with acceptable complication rates and thus might be an option for improving clinical management of iWONde. Trial registration This study is registered with Chinese Clinical Trial Registry (chictr.org.cn number, ChiCTR1800016950).

An eight-week feeding trial was conducted to investigate the effects of chicken gut meal (CGM) in experimental diet on growth performance, plasma biochemical parameters, digestive enzymes activity, intestinal morphologic, muscle composition, and fillet quality of common carp (Cyprinus carpio) (initial body weight: 57.34 ± 0.13 g). Experimental fish were fed with experimental diets containing CGM at 0% (CGM 0 group), 5% (CGM 5% group), 10% (CGM 10% group), 15% (CGM 15% group), and 100% (CGM 100% group) levels, respectively. The results revealed that CGM significantly improved final body weight (FBW), weight gain rate (WGR), specific growth rate (SGR), and feed conversion ratio (FCR) (P

Background. Electrocautery-enhanced lumen-apposing metal stents (ECE-LAMS) have been newly developed to perform EUS-guided choledochoduodenostomy (EUS-CDS), but its benefits and harms remain obscure. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of EUS-CDS using ECE-LAMS. Method. In the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), we searched PubMed, Embase, and Scopus databases through January 1, 2001, and April 27, 2020. The primary outcomes of the pooled analysis were to determine the technical success, clinical success, and overall adverse events rates. The secondary outcomes were pooled rates of short-term and long-term adverse events. Results. Six studies with 270 patients were finally included in this meta-analysis. The pooled rates of technical, clinical success, and adverse events were 95.1% (95% CI = 90.6–97.5%, I2 = 25%), 93.3% (95% CI = 87.4–96.5%, I2 = 28%), and 15.3% (95% CI = 10.6–21.6%, I2 = 13%), respectively. The pooled rates of short-term and long-term adverse events were 3.6% (95% CI = 1.3–9.6%, I2 = 0%) and 11.3% (95% CI = 7.6–16.5%, I2 = 0%), respectively. Conclusion. EUS-CDS using ECE-LAMS provides favorable outcomes in patients with biliary obstruction. It has been associated with a higher success rate and a lower rate of adverse events when compared with the biliary drainage approaches previously used. Large and randomized controlled observational studies are required to further refine the findings in the present analysis.

BACKGROUND:The prevalence of BRCA1/2 variants in Chinese breast cancer patients varies among studies. Germline or somatic BRCA1/2 mutations are associated with sensitivity to poly(ADP-ribose) polymerase-1 inhibitors and DNA-damaging agents. We aimed to investigate the distribution of both somatic and germline BRCA1/2 variants in unselected Chinese breast cancer patients, and explore their roles in tumor phenotype and disease prognosis. METHODS:507 breast cancer patients, unselected for family history of breast cancer or age at diagnosis, were prospectively enrolled from West China Hospital between Feb. 2008 and Feb. 2014. BRCA1/2 variants in the exons/flanking regions were detected in fresh-frozen tumors using next-generation sequencing and confirmed by independent methods. Germline/somatic status was validated by Sanger sequencing in paired blood/normal tissue. RESULTS:BRCA1/2 pathogenic or likely pathogenic (P/LP) variants were detected in 50 patients (9.9%), including 40 germline carriers (18 in BRCA1, 22 in BRCA2), 9 patients with somatic variants (3 in BRCA1, 6 in BRCA2), and 1 patient with concurrent germline/somatic variants in BRCA2. The triple-negative (21.4%) and Luminal B (9.7%) subtypes had higher rates of BRCA1/2 variants. In patients with disease stage 0~II, presence of a germline or somatic BRCA1 P/LP variant increased the risk of relapse as compared to non-carriers [univariate hazard ratio (HR): 3.70, P = 0.04]. Germline BRCA1 P/LP variants, which were associated with aggressive tumor phenotypes, predicted worse disease-free survival in the subgroup of stage 0~II (HR: 4.52, P = 0.02) and N0 (HR: 5.4, P = 0.04) compared to non-carriers. CONCLUSION:A high frequency of germline and somatic BRCA1/2 P/LP variants was detected in unselected Chinese breast cancer patients. Luminal B subtype should be considered as a high-risk population of BRCA1/2 mutation, in addition to triple-negative breast cancer. BRCA1 status was associated with aggressive tumor phenotype and worse disease progression in early stage breast cancer patients.