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Purpose of reviewTo review the current status and ideal time interval of the combination therapy of transarterial chemoembolization (TACE) and local ablation for patients with HCCs.Recent findingsIn recent years, local ablation has been proposed as an alternative curative treatment in the management of HCC. Additionally, many treatment options are available including TACE molecular targeted agents and immune checkpoint inhibitors. Similar overall survival rates and prognoses have been obtained with radiofrequency ablation (RFA) microwave ablation (MWA) and cryoablation for patients with HCCs up to 3 cm in diameter. Yet, MWA has shown superiority in treating large HCCs while cryoablation has several advantages compared with RFA or MWA. Furthermore, the treatment strategy of TACE combined with local ablation is widely accepted by many physicians in order to further increase the survival rate and improve the prognosis of patients with HCCs. However, the time interval between the two sessions of combination therapy remains uncertain in the current guidelines.SummaryCombination therapy of TACE and local ablation has advantages on survival and prognosis in patients with HCC compared with monotherapy. Good patient selection for the right modality needs to be carried out to guarantee the most efficacious treatment for HCC patients. Further studies are needed to find the ideal time interval between TACE and local ablation for HCC patients.

Background Gallbladder carcinoma (GBC) is an extremely aggressive tumor of the biliary tract with a bleak prognosis, and the evidence supporting the benefit of available systemic therapy for advanced GBC is scarce. Herein, this study intended to investigate the real-world outcome of chemotherapy combined with programmed death-1 (PD-1) inhibitor for the management of unresectable or recurrent GBC. Methods From January 2018 to December 2023, consecutive patients who were treated with systematic treatment, including chemotherapy or the combination of chemotherapy plus PD-1 inhibitor, for unresectable or recurrent GBC were retrospectively identified. Clinical data regarding baseline characteristics, therapeutic response, adverse events (AEs), and oncological outcomes were collected. Results The eligible patients were allocated to combination therapy arm ( n  = 46) and mono-chemotherapy arm ( n  = 19). After propensity score matching (PSM), 16 patients were allocated in each arm. The overall survival (OS) and progression-free survival (PFS) of combination therapy were marginally superior to mono-chemotherapy both before and after PSM. The combination therapy exhibited advantage over mono-chemotherapy in regards to partial response (PR) (before PSM: P  = 0.009; after PSM: P  = 0.037) and objective response rate (ORR) (before PSM: P  = 0.006; after PSM: P  = 0.015). In combined therapy cohort, 1 patient achieve a complete response, and 13 patients were assessed as appropriate for surgical excision, among which 1 patient refused further surgical intervention. Conclusions In patients with unresectable or recurrent GBC, the combination of chemotherapy and PD-1 inhibitor as first-line therapy exhibited prolonged OS and PFS, and increased PR and ORR over those receiving chemotherapy alone, with an acceptable toxicity profile. The combination therapy may be a potential conversion therapy in unresectable GBC patients.

(1) Background: Tolypocladium spp. are fungi known for producing cyclosporin A and their ability to infect insects. However, their pathogenicity against the lepidopteran pest Plutella xylostella has not been previously reported. (2) Methods: Four Tolypocladium strains were isolated from soil and identified through morphological and phylogenetic analyses (ITS, gene sequencing). Growth rates, sporulation capacity, and stress tolerance (45 °C heat, UV) were evaluated. Pathogenicity was assessed via larval bioassays, and immune responses were analyzed by quantifying Toll pathway gene expression and enzyme activities (PO, CAT, POD, GSTs, CarE, AChE) from 24 to 96 h post-inoculation. (3) Results: Strains N8-SF-04092 and O1/O2/O3-SF-04630/04927/04931 were identified as Tolypocladium cylindrosporum and Tolypocladium inflatum, respectively. Strain O2 showed the highest growth rate (p < 0.05), while O3 and N8 exhibited superior sporulation (>7 × 105 spores/mm2). N8 also demonstrated notable thermotolerance. In pathogenicity assays, O1, O3, and N8 caused 98.3%, 93.3%, and 96.7% larval mortality, respectively, with LT50 values (3.89–4.45 days) significantly lower than O2 (p < 0.05). Immune gene expression in P. xylostella was transiently activated at 24 h but suppressed from 48 to 96 h by N8 (p < 0.05), while O1 induced partial activation at 24 h and 96 h but suppression at 48 h and 72 h. Protective enzymes (PO, CAT) were initially upregulated (24–48 h) but inhibited after 72 h (p < 0.01). POD activity showed opposing trends between O1 (initially activated then suppressed) and N8 (initially suppressed then activated). Detoxification enzymes (GSTs, CarE, AchE) were predominantly suppressed, except for GSTs, which increased at 72–96 h. (4) Conclusions: Strains O1 and N8 exhibit high virulence against P. xylostella by disrupting immune responses through dynamic modulation of Toll pathway genes and enzyme activities. The thermotolerance of strain N8 further enhances its promising biocontrol agent for field application.

ObjectivesBased on an artificial intelligence approach, this study attempted to establish prognostic models to predict 3-month overt hepatic encephalopathy (OHE) occurrence, 1-year mortality, and liver dysfunction for cirrhotic patients with acute variceal bleeding (AVB) treated with early transjugular intrahepatic portosystemic shunt (TIPS) creation.Materials and MethodsThis retrospective study included patients treated with early TIPS between January 2016 and November 2019. Independent risk factors associated with occurrence of OHE within 3 months, 1-year mortality, and liver dysfunction after early TIPS were identified using univariate and multivariate logistic analyses. Artificial neural network (ANN) models and prognostic nomograms based on the independent risk factors were established and validated internally.ResultsA total of 207 patients were included, with 33 (15.9%) experienced OHE within 3 months after TIPS creation. The albumin-bilirubin grade (P = 0.015), age (≤ 65, > 65 years) (P < 0.001), gender (P = 0.002), and alcoholic cirrhosis (P = 0.013) was identified as independent risk factors associated with 3-month OHE. Presence of portal vein thrombosis (P = 0.034) and model for end-stage liver disease score (P = 0.063) were identified as independent risk factors associated with 1-year mortality. The platelet-albumin-bilirubin grade (P = 0.041) and a history of hepatic encephalopathy (P = 0.018) were identified as independent risk factors associated with liver dysfunction after TIPS creation. Three ANN models and three nomograms were then established and validated with high accuracy.ConclusionsThe ANN and nomogram models have potential to accurately predict early occurrence of OHE, mortality, and liver dysfunction after early TIPS creation for cirrhotic patients with AVB.

Background To detect the right atrial (RA) functions in hypertrophic cardiomyopathy (HCM) patients by using volume-derived values and two-dimensional strain. Methods Thirty-two HCM patients and 34 age and gender matched normal controls were enrolled for this study. RA volume-derived values were measured by using 2D ultrasonic images. RA strain (S-reservoir, S-conduit, S-booster pump) and strain rate (SR-reservoir, SR-conduit, SR-booster pump), representing the reservoir, conduit and booster pump functions, respectively, were measured by EchoPAC. Results Total RA emptying fraction (RAEF) and RA expansion index in HCM patients were significantly lower than normal controls ( p  < 0.05). The values of S-reservoir, S-conduit, Sr-reservoir and Sr-conduit in HCM patients were significantly lower than normal controls ( p  < 0.001). Although there were no significant differences in S-booster pump and Sr-booster pump between HCM patients and normal controls, the absolute values in HCM patients were lower than normal controls. Conclusions In this study, we concluded that RA dysfunctions, including the reservoir and conduit functions were impaired in HCM patients.

Vibrio harveyi is one of the most serious bacterial pathogens to aquatic animals worldwide. Evidence is mounting that coinfections caused by multiple pathogens are common in nature and can alter the severity of diseases in marine animals. However, bacterial coinfections involving V. harveyi have received little attention in mariculture. In this study, the results of pathogen isolation indicated that bacterial coinfection was a common and overlooked risk for hybrid groupers (♀ Epinephelus polyphekadion × ♂ E. fuscoguttatus) reared in an industrialized flow-through pattern in Hainan Province. The artificial infection in hybrid groupers revealed that coinfections with V. harveyi strain GDH11385 (a serious lethal causative agent to groupers) and other isolated pathogens resulted in higher mortality (46.67%) than infection with strain GDH11385 alone (33.33%), whereas no mortality was observed in single infection with other pathogens. Furthermore, the intestine, liver and spleen of hybrid groupers are target organs for bacterial coinfections involving V. harveyi. Based on the infection patterns found in this study, we propose that V. harveyi may have a specific spatiotemporal expression pattern of virulence genes when infecting the host. Taken together, bacterial coinfection with V. harveyi is a neglected high-risk lethal causative agent to hybrid groupers in the industrialized flow-through aquaculture systems in Hainan Province.

Immune checkpoint inhibitors (ICIs) are widely used for treating hepatocellular carcinoma (HCC), yet their efficacy remains limited, with suboptimal response rates. The predictive power of the current biomarker, programmed death ligand‐1 (PD‐L1), is limited by detection variability and glycosylation, underscoring the need for complementary biomarkers to enhance predictive accuracy. In this study, mass spectrometry was employed to identify proteomic alterations in HCC tissues from responders and nonresponders to anti‐programmed cell death‐1 (PD‐1) therapy. Survival analysis established the role of Yin Yang 1 (YY1) in determining ICI efficacy. Coculture models of hepatoma and CD8+ T cells revealed the immunosuppressive function of YY1. Transcriptome sequencing identified polypeptide N‐acetylgalactosaminyltransferase 16 (GALNT16) as a transcriptional target of YY1, and subsequent Western blot and coimmunoprecipitation assays demonstrated that GALNT16 augments PD‐L1 expression. Furthermore, in vivo mouse models demonstrated that YY1 knockdown potentiated the efficacy of anti‐PD‐1 therapy, an effect that was partially reversed by GALNT16 overexpression. Specifically, YY1 upregulates GALNT16, which in turn promotes PD‐L1 glycosylation and stability, leading to diminished CD8+ T cell activity. Thus, GALNT16 knockdown rescued the compromised CD8+ T cell cytotoxicity induced by YY1. Collectively, these results elucidate the YY1/GALNT16/PD‐L1 axis as a pivotal mechanism underlying HCC resistance to ICI therapy. This highlights the therapeutic potential of targeting PD‐L1 glycosylation pathways. Mass‐spectrometric profiling of tumor tissues from anti‐PD‐1‐responsive versus non‐responsive HCC patients identified the transcription factor YY1 as a key regulator. YY1 transcriptionally upregulates the glycosyltransferase GALNT16, which binds PD‐L1 and catalyzes N219 glycosylation. This posttranslational modification stabilizes PD‐L1 on the cell surface, thereby enhancing its interaction with PD‐1 on CD8+ T cells, promoting effector‐cytokine secretion (e.g., IFNγ) and potentiating cytotoxic activity (e.g., upregulation of CD107a) in CD8+ T cells, and ultimately impairing the efficacy of anti‐PD‐1 therapy.

Aim This study aims to develop a five‐dimensional skin color evaluation system and analyze the characteristics of Chinese women’s skin color across these dimensions, focusing on age and key change points. The findings will provide scientific evidence for personalized skin tone management for Chinese women. Method Using noninvasive skin parameter measurements and image processing, 13 facial skin color parameters were collected from 300 Chinese women aged between 18 and 60. A correlation analysis was used to verify the construct validity of the system, exploring interrelationships within and between dimensions. Additionally, polynomial fitting was used to model the five‐dimensional skin tone characteristics by age, and ANOVA was used to assess these characteristics across different age stages. Results Skin pigmentation issues in the Chinese female population are categorized into five dimensions: T (skin tolerance), M (skin moisturizing), U (uniformity of skin color), O (skin optical transmittance), and B (skin brightness). T reflects the skin’s ability to respond to stimuli, while M indicates optimal skin hydration and sebum production. U assesses skin color uniformity, O measures light diffusion within the skin, and B indicates the light reflection intensity of the skin. Correlation analysis suggests that poor tolerance (T) may relate to inadequate moisturization (M), and that U, O, and B positively influence each other. The study identified four different stages of skin color changes in the female population aged between 18 and 60: latent stage (18–25), pigmentation appearance (26–30), accelerated pigmentation (31–43), and pigmentation explosion (44–60). ANOVA results show that Chinese women of varying ages exhibit divergent five‐dimensional skin color characteristics, with a common issue of uneven skin tone observed in all participants. Conclusion The five‐dimensional skin color evaluation system provides an objective method for assessing changes in Chinese women’s skin with age. Dimensions T and M reflect skin condition and underpin management practices, while U, O, and B represent skin tone. As women age, skin pigmentation problems become more noticeable, with an increase in pigmented spots, a decline in translucency, and increased skin unevenness. The most dramatic change occurs during the accelerated pigmentation period between the ages of 31 and 43.

Immunotherapy has shown a modest clinical benefit in advanced hepatocellular carcinoma (HCC), probably due to tumor immunosuppressive functions. Although Notch1 signaling has been implicated in tumor immune escape, its underlying mechanism is unclear. Here, Notch1 signaling is established as a determinant of immunotherapy efficacy in HCC. Studies showed that high Notch1 expression correlates with poor progression‐free survival and worse immunotherapeutic response in recurrent HCC patients, while Notch1 overexpression promotes cancer cell escape by inhibiting CD8 + T cell activation. Mechanistically, Notch1 overexpression upregulates the expression of transcriptional factor YY1 (Yin‐Yang 1), which in turn represses ICAM1 expression to prohibit CD8 + T cell‐derived granzyme‐driven cancer cell pyroptosis and cytotoxicity. Finally, co‐administration of a PD‐L1 antibody with PEI‐siYY1 represses HCC tumor growth without causing severe adverse effects, as observed with the Notch1 inhibitor DAPT. The results establish that targeting Notch1‐YY1‐ICAM1 signaling axis may enhance immunotherapy efficacy by activating CD8 + T cell‐driven cancer cell pyroptosis, providing a safe and effective treatment strategy for HCC patients.

The combination of stent insertion and single high-dose brachytherapy is a feasible and safe palliative treatment regimen in patients with unresectable oesophageal cancer. We aimed to further assess the efficacy of this treatment strategy compared to a conventional covered stent in patients with dysphagia caused by unresectable oesophageal cancer. In this multicentre, single-blind, randomised, phase 3 trial, we enrolled patients with unresectable oesophageal cancer from 16 hospitals in China. We included adult patients (aged ≥ 20 years) with progressive dysphagia, unresectable tumours due to extensive lesions, metastases, or poor medical condition, and with clear consciousness, cooperation, and an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-3. Eligible patients were randomly assigned (in 1:1 ratio, no stratification) to receive either a stent loaded with (125)iodine radioactive seeds (irradiation group) or a conventional oesophageal stent (control group). The primary endpoint was overall survival. Survival analyses were done in a modified intention-to-treat group. This study is registered with ClinicalTrials.gov, number NCT01054274. Between Nov 1, 2009, and Oct 31, 2012, 160 patients were randomly assigned to receive treatment with either an irradiation stent (n=80) or a conventional stent (n=80). During a median follow-up of 138 days (IQR 72-207), 148 stents (73 in the irradiation group and 75 in the control group) were successfully placed into the diseased oesophagus in 148 participants. Median overall survival was 177 days (95% CI 153-201) in the irradiation group versus 147 days (124-170) in the control group (p=0.0046). Major complications and side-effects of the treatment were severe chest pain (17 [23%] of 73 patients in the irradiation group vs 15 [20%] of 75 patents in the control group), fistula formation (six [8%] vs five [7%]), aspiration pneumonia (11 [15%] vs 14 [19%]), haemorrhage (five [7%] vs five [7%]), and recurrent dysphagia (21 [28%] vs 20 [27%]). In patients with unresectable oesophageal cancer, the insertion of an oesophageal stent loaded with (125)iodine seeds prolonged survival when compared with the insertion of a conventional covered self-expandable metallic stent.