Identification of dietary factors that impact the gut microbiota associated with vitiligo: A Mendelian randomization study and meta-analysis.

Previous observational studies have suggested that gut microbiota might be associated with vitiligo. However, owing to the limitations in observational studies of reverse causality and confounders, it remains unclear that whether and how the causal relationships exist. The results suggested that pylum.Bacteroidetes, family.BacteroidalesS24.7, genus.LachnospiraceaeND3007, genus.Marvinbryantia are protective factors for vitiligo. Conversely, family.Lachnospiraceae, order.Burkholderiales, genus.Adlercreutzia, genus.Catenibacterium and genus.Lachnospira are risk factors for vitiligo. In addition, the causative connection between dietary factors and the gut microbiota associated with vitiligo was also investigated. The results revealed that 'alcohol intake versus 10 years pervious' results in a reduction in the abundance of genus.Lachnospiraceae ND3007 and family.BacteroidalesS24.7, bread intake leads to a reduction of genus.Marvinbryantia, 'average weekly red wine intake' is linked to a decrease in the abundance of order.Burkholderiales, tea intake is associated with an augmentation in the abundance of genus.Catenibacterium, salad/raw vegetable intake elevates the abundance of order.Burkholderiales. In summary, this Mendelian randomization study substantiates potential causal effects of gut microbiota on vitiligo. Modulating the gut microbiota through regulating dietary composition may be a novel strategy for preventing vitiligo.

Survival Benefit of Lenvatinib Plus PD-1 Inhibitor with or Without HAIC in Advanced Hepatocellular Carcinoma Beyond Oligometastasis: a Multicenter Cohort Study.

Purpose: The outcome between Lenvatinib plus programmed cell death protein-1 (PD-1) inhibitor and Lenvatinib in HCC beyond oligometastasis was unclear. In this multicenter, we compared the prognosis of Lenvatinib plus PD-1 inhibitor with Lenvatinib in HCC beyond oligometastasis. Patients and Methods: A total of 296 patients from six institutions were included. The patients were divided into two groups: (a) concurrent Lenvatinib plus PD-1 inhibitor treatment (Len+PD-1 group) and (b) Lenvatinib monotherapy (Len group). The primary endpoint was overall survival (OS), the second endpoint was progression-free survival (PFS) and efficacy. Results: The median OS was 20.1 ± 1.2 (17.7-22.5) months and 15.7 ± 1.5 (12.8-18.6) months in the Len+PD-1 and Len groups, respectively. The 12-, 24-, and 36-month OS rates were 79.1%, 39.4%, and 10.7% in the Len+PD-1 group, and 76.3%, 29.7%, and 0% in the Len group, respectively. The OS and PFS rates of the Len+PD-1 group were significantly longer compared with the Len group (hazard ratio [HR], 0.88; 95% confidence index [CI], 0.49-0.94; P = 0.021) and (HR, 0.66; 95% CI, 0.50-0.87; P = 0.003). A subgroup analysis revealed that OS (HR, 0.57; 95% CI, 0.36-0.90; P = 0.016) was improved between the Len+PD-1 and Len groups with hepatic artery infusion chemotherapy (HAIC) treatment, whereas OS (HR, 1.11; 95% CI, 0.68-1.80; P = 0.689) was similar between the Len and Len+PD-1 groups without HAIC. Conclusion: Lenvatinib combined with PD-1 inhibitor significantly improves the survival of HCC beyond oligometastasis. For patients with HAIC, there was obviously significance between Len and Len+PD-1 groups.

Lenvatinib as one of system therapy, is recommended treatment for HCC with multimetastases. The LEAP-002 trial, which evaluated Lenvatinib combined with Pembrolizumab exhibited improved progression-free survival (PFS) and overall survival (OS) compared with Lenvatinib alone. However, the combination efficacy on HCC beyond oligometastasis is unknown. In this multicenter study, we found that Lenvatinib combined with PD-1 inhibitor significantly improved both the OS and PFS and this combination could be recommended for HCC beyond oligometastases. OS and PFS were improved in the Len+PD-1 versus the Len group with hepatic artery infusion chemotherapy (HAIC) treatment, whereas the OS and PFS were similar between the Len and Len+PD-1 groups without HAIC. We provided clinical value that HAIC could be recommended as an effective local therapy to improve the prognosis for advanced HCC.

A Prospective, Single-Arm, Phase 2 Study of Modified Transarterial Chemoembolization Using Low-Dose Chemotherapy with Blank Microspheres Plus Low-Dose Lenvatinib and Microwave Ablation in Patients with Large (≥7 cm) Unresectable Hepatocellular Carcinoma: The TALEM Trial.

Introduction: For patients with large unresectable hepatocellular carcinoma (HCC), the effectiveness of conventional transarterial chemoembolization (cTACE) remains suboptimal. This study investigated the efficacy and safety of modified TACE using low-dose chemotherapy with blank microspheres (BMS-TACE) plus low-dose lenvatinib (LD-LEN) and microwave ablation (MWA) in patients with large unresectable HCC. Methods: In this prospective, single-arm, phase 2 study, patients with unresectable HCC exceeding the up-to-seven criteria, with maximum tumor diameter ≥7 cm, and without macrovascular invasion or extrahepatic metastases, received initial BMS-TACE (lipiodol, low-dose doxorubicin, and lobaplatin up to 30 mg each, and blank microspheres; subsequently modified and repeated in most patients) plus LD-LEN (4-8 mg/day) and MWA. The primary endpoint was downstaging rate (DSR); secondary endpoints were objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events. Results: From November 2019 to March 2022, 43 patients were enrolled. Median follow-up was 21.2 months. Median largest tumor diameter was 11.2 cm (interquartile range [IQR], 7-25). Following BMS-TACE and LD-LEN, downstaging occurred in 37 (86.0%) patients, 32 of whom received MWA, and 8 of whom had a complete response (CR) without MWA. ORR was 93.0% (CR in 32 [74.4%] and partial response in 8 [18.6%] patients). The 1-, 2-, and 3-year PFS rates were 57.5%, 25.9%, and 18.1%, respectively (median PFS, 14.7 months [95% CI: 8.1-19.5]). The 1-, 2-, and 3-year OS rates were 85.8%, 67.7%, and 61.6%, respectively (median OS, 36.4 months [95% CI: 26.8-not reached]). After BMS-TACE, a significant decline in CD11b+/CD33+/HLA-DR- myeloid-derived suppressor cells and early elevation in CXCR5+/CD8+ and CXCR5+/CD4+ T cells were observed (both p < 0.05). Conclusion: BMS-TACE plus LD-LEN and MWA resulted in promising efficacy and tolerable toxicity in patients with large unresectable HCC exceeding the up-to-seven criteria with a maximum tumor diameter ≥7 cm and without macrovascular invasion or extrahepatic metastases.

Polycyclic aromatic hydrocarbons exposure associated with increased risk of psoriasis.

Psoriasis is considered to be multifactorial, with both genetic and environmental factors contributing to its development. Polycyclic aromatic hydrocarbons (PAHs) are widespread in the environment, originating from sources such as cigarette smoke, exhaust emissions, grilled foods, smoked foods and urban air. Researchs have established a link between PAHs exposure and autoimmune disorders; however, specific effects of PAHs on psoriasis remain underexplored. This study aims to evaluate the correlation between PAHs exposure and susceptibility to psoriasis. We analysed eight monohydroxy PAHs (1-Hydroxynaphthalene (1-NAP), 2-Hydroxynaphthalene (2-NAP), 3-Hydroxyfluorene (3-FLU), 2-Hydroxyfluorene (2-FLU), 1-Hydroxyphenanthrene (1-PHE), 1-Hydroxypyrene (1-PYR), 2-Hydroxyphenanthrene (2-PHE) and 3-Hydroxyphenanthrene (3-PHE)) in 5996 participants from the National Health and Nutrition Examination Survey (NHANES). We employed multivariate logistic regression, trend analysis, weighted quantile sum (WQS) regression and restricted cubic spline (RCS) analysis to investigate the relationship between PAHs exposure and psoriasis risk. Multivariate logistic regression and trend analysis revealed that monohydroxy PAHs, including 2-NAP, 3-FLU, 2-FLU and the mixture of 2-PHE and 3-PHE, are associated with an increased risk of psoriasis. Additionally, WQS regression showed a significant positive correlation between combined exposure to monohydroxy PAHs and psoriasis risk, with the mixture of 2-PHE and 3-PHE (47.3%) being the most influential factor. RCS regression further corroborated these findings. Specifically, 2-FLU can increase the expression of psoriasis-related inflammatory factors in HaCaT cells. In conclusion, PAHs exposure increases the risk of developing psoriasis. Efforts to reduce PAHs levels in the environment and minimise exposure are crucial for public health strategies aimed at preventing psoriasis.

The amino acid transporter SLC16A10 promotes melanogenesis by facilitating the transportation of phenylalanine.

Phenylalanine is a crucial amino acid in the process of melanogenesis. However, the exact mechanism by which it is transported into melanocytes has not been disclosed. The aim of this study was to identify and examine the key transporters that are responsible for phenylalanine transportation and evaluate their significance in melanogenesis. The amino acid transporter SLC16A10 was found to be up-regulated in both melasma (GSE72140) and sun-exposed skin (GSE67098). The protein levels of SLC16A10 were proportional to the melanin content in melanocytic nevi, indicating that SLC16A10 was related to melanogenesis. After SLC16A10 overexpression, melanin increased significantly in MNT1 cells. Meanwhile, the expression of melanogenesis-related proteins such as TYR and TYRP1 increased, while their RNA levels did not change. Transcriptomics data indicated that SLC16A10 can enhance the function of ribosome. Furthermore, targeted metabolomics data and ELISA results demonstrated SLC16A10 mainly affected the transport of phenylalanine into the cells. Then, phenylalanine was added to the cell culture medium after SLC16A10 overexpression, melanin synthesis in cells furtherly increased, which verified that SLC16A10 enhances melanogenesis by promoting the uptake of phenylalanine. Finally, we found that SLC16A10 expression increased after UVB irradiation. Knockdown SLC16A10 reduced UVB-induced melanin production and phenylalanine uptake by cells. In summary, SLC16A10 enhances melanogenesis by promoting the uptake of phenylalanine, and upregulation SLC16A10 is likely responsible for the UVB-induced hyperpigmentation as well.

USP26 suppresses type I interferon signaling by targeting TRAF3 for deubiquitination.

Deubiquitinating enzymes (DUBs) play a pivotal role in regulating the antiviral immune response by targeting members of the RLR signaling pathway. As a pivotal member of the RLR pathway, TRAF3 is essential for activating the MAVS/TBK-1/IRF3 signaling pathway in response to viral infection. Despite its importance, the function of DUBs in the TRAF3-mediated antiviral response is poorly understood. Ubiquitin-specific protease 26 (USP26) regulates the RLR signaling pathway to modulate the antiviral immune response. The results demonstrate that EV71 infection upregulates the expression of USP26. Knockdown of USP26 significantly enhances EV71-induced expression of IFN-ß and downstream interferon-stimulated genes (ISGs). Deficiency of USP26 not only inhibits EV71 replication but also weakens the host's resistance to EV71 infection. USP26 physically interacts with TRAF3 and reduces the K63-linked polyubiquitination of TRAF3, thereby promoting pIRF3-mediated antiviral signaling. USP26 physically interacts with TRAF3 and reduces the K63-linked polyubiquitination of TRAF3, thereby promoting pIRF3-mediated antiviral signaling. Conversely, knockdown of USP26 leads to an increase in the K63-linked polyubiquitination of TRAF3. These findings unequivocally establish the essential role of USP26 in RLR signaling and significantly contribute to the understanding of deubiquitination-mediated regulation of innate antiviral responses.

miR-20a: a key regulator of orthodontic tooth movement via BMP2 signaling pathway modulation.

AIM: In this study, we aimed to establish a rat tooth movement model to assess miR-20's ability in enhancing the BMP2 signaling pathway and facilitate alveolar bone remodeling. METHOD: 60 male SD rats had nickel titanium spring devices placed between their left upper first molars and incisors, with the right side serving as the control. Forces were applied at varying durations (18h, 24h, 30h, 36h, 42h, 1d, 3d, 5d, 7d, 14d), and their bilateral maxillary molars and surrounding alveolar bones were retrieved for analysis. Fluorescent quantitative PCR was conducted to assess miR-20a, BMP2, Runx2, Bambi and Smad6 gene expression in alveolar bone, and western blot was performed to determine the protein levels of BMP2, Runx2, Bambi, and Smad6 after mechanical loading. RESULT: We successfully established an orthodontic tooth movement model in SD rats and revealed upregulated miR-20a expression and significantly increased BMP2 and Runx2 gene expression and protein synthesis in alveolar bone during molar tooth movement. Although Bambi and Smad6 gene expression did not significantly increase, their protein synthesis was found to decrease significantly. CONCLUSION: MiR-20a was found to be involved in rat tooth movement model alveolar bone remodeling, wherein it promoted remodeling by reducing Bambi and Smad6 protein synthesis through the BMP2 signaling pathway.

Immune checkpoint inhibitors and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors with or without transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma (CHANCE2201): a target trial emulation study.

Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC. Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821. Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group. Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile. Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project.

Macrophage migration inhibitory factor mediates skin aging via CD74: Insights from single-cell and bulk RNA sequencing data.

Cell-cell communication is crucial for regulating signaling and cellular function. However, the precise cellular and molecular changes remain poorly understood in skin aging. Based on single-cell and bulk RNA data, we explored the role of cell-cell ligand-receptor interaction in skin aging. We found that the macrophage migration inhibitory factor (MIF)/CD74 ligand-receptor complex was significantly upregulatedin aged skin, showing the predominant paracrine effect of keratinocytes on fibroblasts. Enrichment analysis and in vitro experiment revealed a close association of the activation of the MIF/CD74 with inflammatory pathways and immune response. Mechanistically, MIF/CD74 could significantly inhibit PPARγ protein, which thus significantly increased the degree of fibroblast senescence, and significantly up-regulated the expression of senescence-associated secretory phenotype (SASP) factors and FOS gene. Therefore, our study reveals that MIF/CD74 inhibits the activation of the PPAR signaling pathway, subsequently inducing the production of SASP factors and the upregulation of FOS expression, ultimately accelerating fibroblast senescence.

Clinical outcomes of coronavirus disease in patients with breast cancer treated with granulocyte colony-stimulating factor following chemotherapy: Triangulation of evidence using population-based cohort and Mendelian randomization analyses.

Recombinant human granulocyte colony-stimulating factor (G-CSF) administration in patients with cancer and coronavirus disease (COVID-19) remains controversial. Concerns exist that it may worsen COVID-19 outcomes by triggering an inflammatory cytokine storm, despite its common use for managing chemotherapy-induced neutropenia (CIN) or febrile neutropenia post-chemotherapy. Here, we determined whether prophylactic or therapeutic G-CSF administration following chemotherapy exacerbates COVID-19 progression to severe/critical conditions in breast cancer patients with COVID-19. Between December 2022 and February 2023, all 503 enrolled breast cancer patients had concurrent COVID-19 and received G-CSF post-chemotherapy, with most being vaccinated pre-chemotherapy. We prospectively observed COVID-19-related adverse outcomes, conducted association analyses, and subsequently performed Mendelian randomization (MR) analyses to validate the causal effect of genetically predicted G-CSF or its associated granulocyte traits on COVID-19 adverse outcomes. Only 0.99% (5/503) of breast cancer patients experienced COVID-19-related hospitalization following prophylactic or therapeutic G-CSF administration after chemotherapy. No mortality or progression to severe/critical COVID-19 occurred after G-CSF administration. Notably, no significant associations were observed between the application, dosage, or response to G-CSF and COVID-19-related hospitalization (all p >.05). Similarly, the MR analyses showed no evidence of causality of genetically predicted G-CSF or related granulocyte traits on COVID-19-related hospitalization or COVID-19 severity (all p >.05). There is insufficient evidence to substantiate the notion that the prophylactic or therapeutic administration of G-CSF after chemotherapy for managing CIN in patients with breast cancer and COVID-19 would worsen COVID-19 outcomes, leading to severe or critical conditions, or even death, especially considering the context of COVID-19 vaccination.

Chemotherapy alone versus chemotherapy plus 125I brachytherapy for the second-line treatment of locally recurrent cervical cancer after/with radical treatment: A propensity score analysis.

Rationale and objectives: The primary aim of this study was to conduct a retrospective comparative analysis of the survival outcomes in patients with recurrent cervical cancer (CC). Specifically, we aimed to compare the efficacy of chemotherapy alone versus the combined approach of chemotherapy and 125I brachytherapy subsequent to the failure of initial chemotherapy treatment. Materials and methods: Patients diagnosed with recurrent CC subsequent to the failure of initial chemotherapy from January 2007 to December 2016 were enrolled from 2 hospitals. These patients were then divided into two groups: Group A, which underwent second-line chemotherapy alone, and Group B, which received both second-line chemotherapy and 125I brachytherapy. The assessment of overall survival (OS) and progression-free survival (PFS) was carried out through propensity score matching (PSM) (1:1), Kaplan-Meier curves, log-rank tests, and Cox proportional hazard regression for survival analysis. Results: A matched cohort comprising 88 patients each in Group A and Group B was included in the study. In Group A, the 1-, 2-, and 3-year cumulative PFS rates were 40.9 %, 15.9 %, and 5.7 % respectively, while in Group B, these rates were significantly higher at 79.5 %, 48.9 %, and 25.0 % (P = 0.003). Similarly, the 1-, 2-, and 3-year cumulative OS rates among Group A were 67.0 %, 27.3 %, and 5.7 % compared to 89.8 %, 63.6 %, and 30.7 % among Group B, suggesting a difference with statistical significance (P < 0.001) between the two groups. Moreover, the incidence of complications was similar between groups (P = 0.698). Conclusions: Our findings suggest that the combined approach of chemotherapy and 125I brachytherapy yields superior therapeutic effects but similar complication rates compared to chemotherapy alone in patients experiencing local recurrence of CC following failed initial chemotherapy.

A bibliometric analysis of literatures on uterine leiomyosarcoma in the last 20 years.

Background: Uterine leiomyosarcoma(uLMS) is a rare malignant tumor with low clinical specificity and poor prognosis.There are many studies related to uLMS, however, there is still a lack of metrological analyses with generalization. This study provides a bibliometric study of uLMS. Methods and materials: We chose the Web of Science (WoS) as our main database due to its extensive interdisciplinary coverage. We specifically focused on the literature from the last 20 years to ensure relevance and practicality. By utilizing the WOS core dataset and leveraging the R package "bibliometric version 4.1.0" and Citespace, we performed a comprehensive bibliometric analysis. This allowed us to pinpoint research hotspots and create visual representations, resulting in the retrieval of 2489 pertinent articles. Results: This literature review covers 2489 articles on uterine leiomyosarcoma (uLMS) from the past 20 years. Key findings include an average annual publication rate of 8.75, with a 6.07% yearly growth rate and an average citation count of 17.22. Core+Zone 2 sources contributed 1079 articles and 207 reviews, displaying a 4.98% annual growth rate. The analysis identified top journals, influential authors, and core sources, such as the prevalence of publications from the United States and the dominance of GYNECOLOGIC ONCOLOGY and HENSLEY ML. Bradford's Law and Lotka's Law highlighted core sources and author productivity, respectively. Thematic mapping and factorial analysis revealed research clusters, including etiology, diagnosis, treatment advancements, and surgical approaches, with prominent themes such as gemcitabine and docetaxel. Overall, this comprehensive analysis provides insights into uLMS literature trends and influential factors. Conclusion: This thorough bibliometric analysis, in its whole, illuminates the field's guiding principles while also revealing the subtle patterns within the uLMS literature. The knowledge gained here contributes to the current discussion in uLMS and related scientific fields and provides a solid basis for future research paths.

Efficacy and influencing factors of CO2 laser, topical photodynamic therapy versus therapy combined with CO2 laser pretreatment for vaginal low-grade squamous intraepithelial lesions with high-risk HPV infection.

BACKGROUND: Vaginal intraepithelial neoplasia (VaIN) is a group of diseases of squamous epithelial dysplasia and carcinoma in situ occurring in the vagina, which is associated with high-risk human papillomavirus (HR-HPV) infection. OBJECTIVES: To evaluate the efficacy and safety of Carbon dioxide (CO2) laser, 5-aminolevulinic acid photodynamic therapy (PDT) and PDT combined with CO2 laser pretreatment for VaIN1 with HR-HPV infection, and analyze the factors affecting the clearance of HR-HPV. METHODS: Patients with HR-HPV infection and pathological diagnosis of VaIN1 and received laser or PDT or PDT combined with laser pretreatment were recruited. A total of 45 patients received one to three times CO2 laser (laser Group), 15 patients received three times PDT (PDT Group) and 15 patients received CO2 laser once and PDT three times (laser + PDT Group). HPV testing, cytology and colposcopy examinations at 3-6 months and 9-12 months after treatment were analyzed to assess the outcomes of the treatment. RESULTS: There was no significant difference in regression rate of VaIN1 among the laser Group, the PDT Group and the laser + PDT Group (3-6 month follow-up: 57.78% vs 73.3% vs 80 %, 9-12 month follow-up: 68.89% vs 80% vs 86.67 %, P>0.05). HR-HPV remission rates were also similar in the three groups (3-6 month follow-up: 26.67% vs 46.67% vs 46.67 %, 9-12 month follow-up: 40 % in all groups, P>0.05). Compared to HR-HPV negative group, patients in the HR-HPV positive group were older and had more pregnancies. Menopause and multiple vaginal lesions were more common in the HR-HPV positive group. Adverse reactions were mild in the PDT Group. The laser Group and the laser + PDT Group had more adverse effects, such as increased vaginal secretion, vaginal bleeding, scarring and local pain. CONCLUSION: For patients with VaIN1 at risk of progression, ALA-PDT presents itself as a viable choice for those who are well-informed and can consent to its costs and benefits. The addition of CO2 laser pretreatment may not increase the benefit of ALA-PDT treatment of VaIN1. Older age, menopause, more times of pregnancies, and multiple vaginal lesions might affect HR-HPV regression.

Transarterial Chemoembolization Combined with Lenvatinib Plus Sequential Microwave Ablation for Large Hepatocellular Carcinoma Beyond Up-to-Seven Criteria: A Retrospective Cohort Study.

RATIONALE AND OBJECTIVES: The aim of this study was to investigate the efficacy and safety of transarterial chemoembolization (TACE) combined with Lenvatinib plus sequential microwave ablation (MWA) for the treatment of patients with large hepatocellular carcinoma (HCC) beyond up-to-seven criteria. MATERIALS AND METHODS: This retrospective cohort study assessed the medical records of patients with large HCC who underwent TACE combined with Lenvatinib plus sequential MWA (TLM) or TACE plus sequential MWA (TM). Lenvatinib was administered to patients within 3-5 days after TACE and sequential MWA was performed once they met the criteria for curative ablation after TACE or the combination therapy. The progression-free survival (PFS), overall survival (OS) and treatment-related complications were compared between two groups. RESULTS: Of the 81 patients who underwent TLM or TM, 64 who met the eligibility criteria were included in this study. Among them, 28 patients underwent TLM and 36 underwent TM. The inverse probability weighting method (IPTW) was used to balance differences between two groups. The TLM group had longer PFS than the TM group (median, before IPTW: 18.53 vs. 5.62 months, p < 0.001; median, after IPTW: 28.27 vs. 5.30 months, p < 0.001). Univariate and multivariate analyses revealed that TLM and the maximum tumor diameter were independent prognostic factors for PFS. The overall incidence rate of minor complications related to TACE or MWA was lower in the TLM group (32.1% vs. 66.7%, p = 0.006). CONCLUSION: TACE combined with Lenvatinib plus sequential MWA can prolong the progression-free survival of patients with large HCC beyond up-to-seven criteria.

Coatings on Lithium Battery Separators: A Strategy to Inhibit Lithium Dendrites Growth.

Lithium metal is considered a promising anode material for lithium secondary batteries by virtue of its ultra-high theoretical specific capacity, low redox potential, and low density, while the application of lithium is still challenging due to its high activity. Lithium metal easily reacts with the electrolyte during the cycling process, resulting in the continuous rupture and reconstruction of the formed SEI layer, which reduces the cycling reversibility. On the other hand, repeated lithium plating/stripping processes can lead to uncontrolled growth of lithium dendrites and a series of safety issues caused by short-circuiting of the battery. Currently, modification of the battery separator layer is a good strategy to inhibit lithium dendrite growth, which can improve the Coulombic efficiency in the cycle. This paper reviews the preparation, behavior, and mechanism of the modified coatings using metals, metal oxides, nitrides, and other materials on the separator to inhibit the formation of lithium dendrites and achieve better stable electrochemical cycles. Finally, further strategies to inhibit lithium dendrite growth are proposed.

Disease Awareness and Treatment Preferences in Vitiligo: A Cross-sectional Study in China.

In China, there is a lack of data regarding the awareness and treatment preferences among patients with vitiligo and their families. To address this gap, a cross-sectional questionnaire-based study was conducted to investigate disease awareness and treatment preferences in Chinese patients with vitiligo. The study also evaluated willingness to pay, using 2 standardized items, and assessed quality of life, using the Dermatology Life Quality Index (DLQI) score. Data from 307 patients with vitiligo (59.3% women, mean age 28.98 years, range 2-73 years) were analysed. Of these patients, 44.7% had insufficient knowledge of vitiligo, particularly those from rural areas or with low levels of education. Mean DLQI total score was 4.86 (5.24 for women and 4.30 for men). Among the most accepted treatments were topical drugs, phototherapy, and systemic therapy. Patients were relatively conservative about the duration and cost of treatment, with only 27.7% willing to pay more than 10,000 Chinese yuan renminbi (CNY) for complete disease remission. High level of education, high income, skin lesions in specific areas, and skin transplantation therapy predicted higher willingness to pay. Insufficient knowledge was associated with a higher burden of disease. In order to reduce the disease burden and improve treatment adherence it is crucial to enhance disease awareness and take into account patient preferences.

An eye tracking investigation of attention mechanism in driving behavior under emotional issues and cognitive load.

Emotions have specific effects on behavior. At present, studies are increasingly interested in how emotions affect driving behavior. We designed the experiment by combing driving tasks and eye tracking. DSM-V assessment scale was applied to evaluate the depression and manic for participants. In order to explore the dual impacts of emotional issues and cognitive load on attention mechanism, we defined the safety-related region as the area of interest (AOI) and quantified the concentration of eye tracking data. Participants with depression issues had lower AOI sample percentage and shorter AOI fixation duration under no external cognitive load. During our experiment, the depression group had the lowest accuracy in arithmetic quiz. Additionally, we used full connected network to detect the depression group from the control group, reached 83.33%. Our experiment supported that depression have negative influences on driving behavior. Participants with depression issues reduced attention to the safety-related region under no external cognitive load, they were more prone to have difficulties in multitasking when faced with high cognitive load. Besides, participants tended to reallocate more attention resources to the central area under high cognitive load, a phenomenon we called "visual centralization" in driving behavior.

The SARS-CoV-2 nucleocapsid protein suppresses innate immunity by remodeling stress granules to atypical foci.

Viruses deploy multiple strategies to suppress the host innate immune response to facilitate viral replication and pathogenesis. Typical G3BP1+ stress granules (SGs) are usually formed in host cells after virus infection to restrain viral translation and to stimulate innate immunity. Thus, viruses have evolved various mechanisms to inhibit SGs or to repurpose SG components such as G3BP1. Previous studies showed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection inhibited host immunity during the early stage of COVID-19. However, the precise mechanism is not yet well understood. Here we showed that the SARS-CoV-2 nucleocapsid (SARS2-N) protein suppressed the double-stranded RNA (dsRNA)-induced innate immune response, concomitant with inhibition of SGs and the induction of atypical SARS2-N+ /G3BP1+ foci (N+ foci). The SARS2-N protein-induced formation of N+ foci was dependent on the ability of its ITFG motif to hijack G3BP1, which contributed to suppress the innate immune response. Importantly, SARS2-N protein facilitated viral replication by inducing the formation of N+ foci. Viral mutations within SARS2-N protein that impair the formation of N+ foci are associated with the inability of the SARS2-N protein to suppress the immune response. Taken together, our study has revealed a novel mechanism by which SARS-CoV-2 suppresses the innate immune response via induction of atypical N+ foci. We think that this is a critical strategy for viral pathogenesis and has potential therapeutic implications.

Camrelizumab (a PD-1 inhibitor) plus apatinib (an VEGFR-2 inhibitor) and hepatic artery infusion chemotherapy for hepatocellular carcinoma in Barcelona Clinic Liver Cancer stage C (TRIPLET): a phase II study.

Hepatic arterial infusion chemotherapy (HAIC) using a combination of oxaliplatin, fluorouracil, and leucovorin (FOLFOX) has shown promise for hepatocellular carcinoma (HCC) patients classified under Barcelona Clinic Liver Cancer (BCLC) stage C. In China, the combined therapy of camrelizumab and apatinib is now an approved first-line approach for inoperable HCC. This study (NCT04191889) evaluated the benefit of combining camrelizumab and apatinib with HAIC-FOLFOX for HCC patients in BCLC stage C. Eligible patients were given a maximum of six cycles of HAIC-FOLFOX, along with camrelizumab and apatinib, until either disease progression or intolerable toxicities emerged. The primary outcome measured was the objective response rate (ORR) based on the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Thirty-five patients were enrolled. Based on RECIST v1.1 criteria, the confirmed ORR stood at 77.1% (95% CI: 59.9% to 89.6%), with a disease control rate of 97.1% (95% CI: 85.1% to 99.9%). The median progression-free survival was 10.38 months (95% CI: 7.79 to 12.45). Patient quality of life had a transient deterioration within four cycles of treatment, and generally recovered thereafter. The most frequent grade ≥3 or above treatment-related adverse events included reduced lymphocyte count (37.1%) and diminished neutrophil count (34.3%). The combination of camrelizumab, apatinib, and HAIC demonstrated encouraging results and manageable safety concerns for HCC at BCLC stage C.