Meta-analysis of transarterial chemoembolization combined with cryoablation vs transarterial chemoembolization alone for ≥ 5 cm hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) ranks sixth globally in cancer incidence and third in mortality rates. Unfortunately, over 70% of HCC patients forego the opportunity for curative surgery or liver transplantation due to inadequate physical examinations, poor physical condition, and limited organ availability upon diagnosis. Clinical guidelines endorse transarterial chemoembolization (TACE) as the frontline treatment for intermediate to advanced-stage HCC. Cryoablation (CRA) is an emerging local ablative therapy increasingly used in HCC management. Recent studies suggest that combining CRA with TACE offers complementary and synergistic effects, potentially improving long-term survival rates. However, the superiority of combined TACE + CRA therapy over TACE alone for HCC lesions equal to or exceeding 5 cm requires further investigation. AIM: To compare the efficacy and safety of TACE combined with CRA vs TACE alone in the treatment of HCC with a diameter of ≥ 5 cm. METHODS: PubMed, EMBASE, Cochrane Library, CNKI, Wanfang, and VIP databases were searched to retrieve all relevant studies on TACE and CRA up to July 2022. Meta-analysis was performed using RevMan 5.3 software. RESULTS: After screening according to the inclusion and exclusion criteria, 6 articles were included, including 2 randomized controlled trials and 4 nonrandomized controlled trials, with a total of 575 patients included in the meta-analysis. The results showed that the objective response rate [odds ratio (OR) = 2.56, 95% confidence interval (CI):1.66-3.96, P < 0.0001), disease control rate (OR = 3.03, 95%CI: 1.88-4.89, P < 0.00001), 1-year survival rate (OR = 3.79, 95%CI: 2.50-5.76, P < 0.00001), 2-year survival rate (OR = 2.34, 95%CI: 1.43-3.85, P = 0.0008), and 3-year survival rate (OR = 3.34, 95%CI: 1.61-6.94, P = 0.001) were all superior to those of the control group; the postoperative decrease in alpha-fetoprotein value (OR = 295.53, 95%CI: 250.22-340.85, P < 0.0001), the postoperative increase in CD4 value (OR = 10.59, 95%CI: 8.78-12.40, P < 0.00001), and the postoperative decrease in CD8 value (OR = 6.47, 95%CI: 4.44-8.50, P < 0.00001) were also significantly higher than those in the TACE-alone treatment group. CONCLUSION: Compared with TACE-alone treatment, TACE + CRA combined treatment not only improves the immune function of HCC patients with a diameter of ≥ 5 cm, but also enhances the therapeutic efficacy and long-term survival rate, without increasing the risk of complications. Therefore, TACE + CRA combined treatment may be a more recommended treatment for patients with HCC with a diameter of ≥ 5 cm.

Single-cell analysis of the survival mechanisms of fratricidal CAR-T targeting of T cell malignancies.

Chimeric antigen receptor T (CAR-T) cell therapy targeting T cell tumors still faces many challenges, one of which is its fratricide due to the target gene expressed on CAR-T cells. Despite this, these CAR-T cells can be expanded in vitro by extending the culture time and effectively eliminating malignant T cells. However, the mechanisms underlying CAR-T cell survival in cell subpopulations, the molecules involved, and their regulation are still unknown. We performed single-cell transcriptome profiling to investigate the fratricidal CAR-T products (CD26 CAR-Ts and CD44v6 CAR-Ts) targeting T cells, taking CD19 CAR-Ts targeting B cells from the same donor as a control. Compared with CD19 CAR-Ts, fratricidal CAR-T cells exhibit no unique cell subpopulation, but have more exhausted T cells, fewer cytotoxic T cells, and more T cell receptor (TCR) clonal amplification. Furthermore, we observed that fratricidal CAR-T cell survival was accompanied by target gene expression. Gene expression results suggest that fratricidal CAR-T cells may downregulate their human leukocyte antigen (HLA) molecules to evade T cell recognition. Single-cell regulatory network analysis and suppression experiments revealed that exhaustion mediated by critical regulatory factors may contribute to fratricidal CAR-T cell survival. Together, these data provide valuable and first-time insights into the survival of fratricidal CAR-T cells.

DCAF7 Acts as A Scaffold to Recruit USP10 for G3BP1 Deubiquitylation and Facilitates Chemoresistance and Metastasis in Nasopharyngeal Carcinoma.

Despite docetaxel combined with cisplatin and 5-fluorouracil (TPF) being the established treatment for advanced nasopharyngeal carcinoma (NPC), there are patients who do not respond positively to this form of therapy. However, the mechanisms underlying this lack of benefit remain unclear. DCAF7 is identified as a chemoresistance gene attenuating the response to TPF therapy in NPC patients. DCAF7 promotes the cisplatin resistance and metastasis of NPC cells in vitro and in vivo. Mechanistically, DCAF7 serves as a scaffold protein that facilitates the interaction between USP10 and G3BP1, leading to the elimination of K48-linked ubiquitin moieties from Lys76 of G3BP1. This process helps prevent the degradation of G3BP1 via the ubiquitin‒proteasome pathway and promotes the formation of stress granule (SG)-like structures. Moreover, knockdown of G3BP1 successfully reversed the formation of SG-like structures and the oncogenic effects of DCAF7. Significantly, NPC patients with increased levels of DCAF7 showed a high risk of metastasis, and elevated DCAF7 levels are linked to an unfavorable prognosis. The study reveals DCAF7 as a crucial gene for cisplatin resistance and offers further understanding of how chemoresistance develops in NPC. The DCAF7-USP10-G3BP1 axis contains potential targets and biomarkers for NPC treatment.

Heat-related illness and dementia: a study integrating epidemiological and experimental evidence.

BACKGROUND: Heat-related illness (HRI) is commonly considered an acute condition, and its potential long-term consequences are not well understood. We conducted a population-based cohort study and an animal experiment to evaluate whether HRI is associated with dementia later in life. METHODS: The Taiwan National Health Insurance Research Database was used in the epidemiological study. We identified newly diagnosed HRI patients between 2001 and 2015, but excluded those with any pre-existing dementia, as the study cohort. Through matching by age, sex, and the index date with the study cohort, we selected individuals without HRI and without any pre-existing dementia as a comparison cohort at a 1:4 ratio. We followed each cohort member until the end of 2018 and compared the risk between the two cohorts using Cox proportional hazards regression models. In the animal experiment, we used a rat model to assess cognitive functions and the histopathological changes in the hippocampus after a heat stroke event. RESULTS: In the epidemiological study, the study cohort consisted of 70,721 HRI patients and the comparison cohort consisted of 282,884 individuals without HRI. After adjusting for potential confounders, the HRI patients had a higher risk of dementia (adjusted hazard ratio [AHR] = 1.24; 95% confidence interval [CI]: 1.19-1.29). Patients with heat stroke had a higher risk of dementia compared with individuals without HRI (AHR = 1.26; 95% CI: 1.18-1.34). In the animal experiment, we found cognitive dysfunction evidenced by animal behavioral tests and observed remarkable neuronal damage, degeneration, apoptosis, and amyloid plaque deposition in the hippocampus after a heat stroke event. CONCLUSIONS: Our epidemiological study indicated that HRI elevated the risk of dementia. This finding was substantiated by the histopathological features observed in the hippocampus, along with the cognitive impairments detected, in the experimental heat stroke rat model.

Mechanistic insights into phosphoactivation of SLAC1 in guard cell signaling.

Stomata in leaves regulate gas (carbon dioxide and water vapor) exchange and water transpiration between plants and the atmosphere. SLow Anion Channel 1 (SLAC1) mediates anion efflux from guard cells and plays a crucial role in controlling stomatal aperture. It serves as a central hub for multiple signaling pathways in response to environmental stimuli, with its activity regulated through phosphorylation via various plant protein kinases. However, the molecular mechanism underlying SLAC1 phosphoactivation has remained elusive. Through a combination of protein sequence analyses, AlphaFold-based modeling and electrophysiological studies, we unveiled that the highly conserved motifs on the N- and C-terminal segments of SLAC1 form a cytosolic regulatory domain (CRD) that interacts with the transmembrane domain(TMD), thereby maintaining the channel in an autoinhibited state. Mutations in these conserved motifs destabilize the CRD, releasing autoinhibition in SLAC1 and enabling its transition into an activated state. Our further studies demonstrated that SLAC1 activation undergoes an autoinhibition-release process and subsequent structural changes in the pore helices. These findings provide mechanistic insights into the activation mechanism of SLAC1 and shed light on understanding how SLAC1 controls stomatal closure in response to environmental stimuli.

Alterations in gut microbiota and inflammatory cytokines after administration of antibiotics in mice.

Antibiotics are widely used to treat bacterial infection and reduce the mortality rate, while antibiotic overuse can cause gut microbiota dysbiosis. The impact of antibiotics on gut microbiota is not fully understood. In our study, four commonly used antibiotics (ceftazidime, cefoperazone-sulbactam, imipenem-cilastatin, and moxifloxacin) were given subcutaneously to mice, and their impacts on the gut microbiota composition and serum cytokine levels were evaluated through 16S rRNA analysis and a multiplex immunoassay. Antibiotic treatment markedly reduced gut microbiota diversity and changed gut microbiota composition. Antibiotic treatment significantly increased and decreased the abundance of Firmicutes and Bacteroidota, respectively. The antibiotic treatments increased the abundance of opportunistic pathogens such as Enterococcus and decreased that of Lachnospiraceae and Muribaculaceae. For moxifloxacin, the significantly high abundance of Enterococcus and Klebsiella was observed after 14 and 21 days of treatment. However, a relatively low abundance of opportunistic pathogens was found after 14 days of imipenem-cilastatin treatment. Additionally, the serum levels of various pro-inflammatory cytokines, such as IL-1ß, IL-12 (p70), and IL-17, significantly increased after 21 days of antibiotic treatments. Overall, these results provide a guide for rational use of antibiotics in clinical settings: short-term use of moxifloxacin is recommended with regard to gut microbiota health, and the 14-day use of imipenem-cilastatin may have a less severe impact than other antibiotics.IMPORTANCEAntibiotic treatments are directly associated with changes in gut microbiota and are effective against both pathogens and beneficial bacteria. Gut microbiota dysbiosis induced by antibiotic treatment could increase the risk of some diseases. Therefore, an adequate understanding of gut microbiota changes after antibiotic use is crucial. In this study, we investigated the effects of continuous treatment with antibiotics on gut microbiota, serum cytokines, and intestinal inflammatory response. Our results suggest that short-term use of moxifloxacin is recommended, and the 14-day use of imipenem-cilastatin may have a less severe effect on gut microbiota health than cefoperazone-sulbactam. These results provide useful guidance on the rational use of antibiotics with regard to gut microbiota health.

Synthesis of High-Quality Bulk Single-Crystal Black Phosphorus by the Circulating Vapor Growth Approach.

Black phosphorus (BP), a promising two-dimensional (2D) layered semiconductor material, has gained enormous attention due to its impressive properties over the past several years. Although plenty of methods have been developed to synthesize high-quality BP, most of the currently available BP materials still suffer from unsatisfactory crystallization, purity, and stability in air, hindering their practical application. A facile approach to synthesizing ultrahigh-quality single-crystal BP is of significance to shed light on the nature of 2D semiconductor materials and their massive application. In this work, we present the facile and efficient circulating vapor growth approach to growing bulk single-crystal BP. The as-grown BP material features high crystallinity and ultrahigh purity (higher than 99.999 at %), exceeding those of all the previously reported and some commercially available BP crystals. It also maintains excellent stability in air and water after 15 consecutive days of test. Moreover, the as-synthesized BP material features good thermal stability, oxidation resistance, and excellent electrical properties, as well. This study provides a new approach for the fabrication of ultrahigh-quality BP material and thus promotes its application.

Exploring the novel benefits of leucine: Protecting nitrite-induced liver damage in sub-adult grass carp (Ctenopharyngodon idella) through regulating mitochondria quality control.

Leucine is an essential amino acid for fish. The ability of leucine to resist stress in fish has not been reported. Nitrite is a common pollutant in the aquatic environment. Therefore, we investigated the effects of dietary leucine on growth performance and nitrite-induced liver damage, mitochondrial dysfunction, autophagy, and apoptosis for sub-adult grass carp. A total of 450 grass carp (615.91 ± 1.15 g) were selected and randomly placed into 18 net cages. The leucine contents of the six diets were 2.91, 5.90, 8.92, 11.91, 14.93, and 17.92 g/kg, respectively. After a 9-week feeding trial, the nitrite exposure experiment was set up for 96 h. These results indicated that dietary leucine significantly promoted FW, WG, PWG, and SGR of sub-adult grass carp (P < 0.05). Appropriate levels of dietary leucine (11.91-17.92 g/kg) decreased the activities of serum parameters (glucose, cortisol, and methemoglobin contents, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and lactate dehydrogenase), the contents of reactive oxygen species (ROS), nitric oxide (NO) and peroxynitrite (ONOO-). In addition, appropriate levels of dietary leucine (11.91-17.92 g/kg) increased the mRNA levels of mitochondrial biogenesis genes (PGC-1α, Nrf1/2, TFAM), fusion-related genes (Opa1, Mfn1/2) (P < 0.05), and decreased the mRNA levels of caspase 3, caspase 8, caspase 9, fission-related gene (Drp1), mitophagy-related genes (Pink1, Parkin) and autophagy-related genes (Beclin1, Ulk1, Atg5, Atg7, Atg12) (P < 0.05). Appropriate levels of dietary leucine (8.92-17.92 g/kg) also increased the protein levels of AMP-activated protein kinase (AMPK), prostacyclin (p62) and decreased the protein levels of protein light chain 3 (LC3), E3 ubiquitin ligase (Parkin), and Cytochrome c (Cytc). Appropriate levels of leucine (8.92-17.92 g/kg) could promote growth performance and alleviate nitrite-induced mitochondrial dysfunction, autophagy, apoptosis for sub-adult grass carp. Based on quadratic regression analysis of PWG and serum GPT activity, dietary leucine requirements of sub-adult grass carp were recommended to be 12.47 g/kg diet and 12.55 g/kg diet, respectively.

Construction of ROS-Responsive Hyaluronic Acid Modified Paclitaxel and Diosgenin Liposomes and Study on Synergistic Enhancement of Anti-Ovarian Cancer Efficacy.

Purpose: Ovarian cancer is a fatal gynecologic malignancy with a high rate of abdominal metastasis. Chemotherapy still has a poor clinical prognosis for ovarian cancer patients, with cell proliferation and angiogenesis leading to invasion, migration, and recurrence. To overcome these obstacles, we constructed a novel HA-modified paclitaxel and diosgenin liposome (PEG-TK-HA-PDLPs) using two novel functional materials, DSPE-PEG2000-HA and DSPE-PEG2000-TK-PEG5000, to specifically deliver the drugs to the tumor site in order to reduce OC cell proliferation and anti-angiogenic generation, thereby inhibiting invasion and migration. Methods and Results: PEG-TK-HA-PDLPs were prepared by film dispersion, with ideal physicochemical properties and exhibits active targeting for enhanced cellular uptake. The ZIP synergy score for PTX and Dios was calculated using the online SynergyFinder software to be 3.15, indicating synergy. In vitro results showed that PEG-TK-HA-PDLPs were highly cytotoxic to ID8 cells, induced ID8 cell apoptosis, and inhibited ID8 cell migration and invasion. In vivo studies showed that PEG-TK-HA-PDLPs could prolong the circulation time in the blood, accumulate significantly in the tumor site, and effectively fight against angiogenesis with significant anti-tumor effects. Conclusion: The production of PEG-TK-HA-PDLPs is an effective strategy for the treatment of OC.

USP47 deficiency in mice modulates tumor infiltrating immune cells and enhances antitumor immune responses in prostate cancer.

This study investigates the role of USP47, a deubiquitinating enzyme, in the tumor microenvironment and its impact on antitumor immune responses. Analysis of TCGA database revealed distinct expression patterns of USP47 in various tumor tissues and normal tissues. Prostate adenocarcinoma showed significant downregulation of USP47 compared to normal tissue. Correlation analysis demonstrated a positive association between USP47 expression levels and infiltrating CD8+ T cells, neutrophils, and macrophages, while showing a negative correlation with NKT cells. Furthermore, using Usp47 knockout mice, we observed a slower tumor growth rate and reduced tumor burden. The absence of USP47 led to increased infiltration of immune cells, including neutrophils, macrophages, NK cells, NKT cells, and T cells. Additionally, USP47 deficiency resulted in enhanced activation of cytotoxic T lymphocytes (CTLs) and altered T cell subsets within the tumor microenvironment. These findings suggest that USP47 plays a critical role in modulating the tumor microenvironment and promoting antitumor immune responses, highlighting its potential as a therapeutic target in prostate cancer.

Enhancing efficacy and reducing toxicity: Therapeutic optimization in locoregionally advanced nasopharyngeal carcinoma.

When applied as the standard therapeutic modality, intensity-modulated radiotherapy (IMRT) improves local control and survival rates in patients with nasopharyngeal carcinoma (NPC). However, distant metastasis continues to be the leading cause of treatment failure. Here, we review the most recent optimization strategies for combining chemotherapy with IMRT in high-risk patients with locoregionally advanced NPC. We focus on major clinical trials on induction chemotherapy and metronomic adjuvant chemotherapy, emphasizing their efficacy in mitigating distant metastasis and prognosis. We also highlight innovations in reducing toxicity in low-risk patients, particularly through approaches of excluding chemotherapy, adopting equivalent low-toxicity drugs, or selectively exempting lymph nodes with low metastatic risk from irradiation. These approaches have provided positive treatment outcomes and significantly enhanced patients' quality of life. Finally, we provide an overview of the evolving immunotherapy landscape, with a focus on the ongoing trials and future potential of immune checkpoint inhibitors in advanced NPC treatment.

Family migration and well-being of Chinese migrant workers' children.

This article aims to explore the effects of parental migration on the well-being of children and how to adjust social cognitive well-being through the interrelations among family relations and social cognitive well-being indicators using structural equation modelling. Two modified social cognitive well-being models were tested in 1682 Chinese migrant workers' children to examine the pathways among social cognitive well-being and family relation characteristics. The modified models are based on the social cognitive well-being model and the characteristics of Chinese migrant workers' children. The results show that caregiver-child communication frequency, caregiver-child regulation, caregiver-child conflicts, caregiver-child trust and communication, and coactivity positively impact children's social cognitive well-being. In contrast, caregiver-child alienation negatively influences children's social cognitive factors through caregiver-child trust and communication. Additionally, this research revealed that family-related characteristics (caregiver-child regulation, caregiver-child coactivities, caregiver-child communication frequency, caregiver-child alienation, caregiver-child conflicts, and caregiver-child trust and communication) are interconnected with social cognitive well-being indicators (academic satisfaction, outcome expectations, goal progress, lifelong satisfaction, environmental support, positive affect, negative affect, and self-efficacy). This suggests that family migration and relationships with caregiver(s) can significantly affect the well-being of migrant workers' children.

Thrombomodulin Improves Cognitive Deficits in Heat-Stressed Mice.

BACKGROUND: Thrombomodulin (TM) exerts anticoagulant and anti-inflammatory effects to improve the survival of patients with septic shock. Heat stroke resembles septic shock in many aspects. We tested whether TM would improve cognitive deficits and related causative factors in heat-stressed mice. METHODS: Adult male mice were exposed to HS (33 oC 2h daily for 7 consecutive days) to induce cognitive deficits. Recombinant human soluble thrombomodulin (TM, 1 mg/kg, i.p.) was administered immediately after the first HS trial and then once daily for 7 consecutive days. We performed the Y-maze, novel objective recognition, and passive avoidance tests to evaluate cognitive function. Plasma levels of lipopolysaccharide, high-mobility group box 1 (HMGB1), coagulation parameters, and both plasma and tissue levels of inflammatory and oxidative stress markers were measured biochemically. The duodenum and hippocampus sections were immunohistochemically stained. The intestinal and blood-brain barrier permeability were determined. RESULTS: Compared to controls, HS mice treated with TM had lesser extents of cognitive deficits, exacerbated stress reactions, gut barrier disruption, endotoxemia, blood-brain barrier disruption, and inflammatory, oxidative, and coagulatory injury to heart, duodenum, and hippocampal tissues, and increased plasma HMGB1. In addition to reducing cognitive deficits, TM therapy alleviated all the abovementioned complications in heat-stressed mice. CONCLUSIONS: The findings suggest that heat stress can lead to exacerbated stress reactions, endotoxemia, gut barrier disruption, blood-brain barrier disruption, hippocampal inflammation, coagulopathy, and oxidative stress, which may act as causative factors for cognitive deficits. Thrombomodulin, an anti-inflammatory, antioxidant, and anti-coagulatory agent, inhibited heat stress-induced cognitive deficits in mice.

Identification of circular RNAs regulating cardiomyocyte proliferation in neonatal pig hearts.

Little is known about the expression patterns and functions of circular RNAs (circRNAs) in the heart of large mammals. In this study, we examined the expression profiles of circRNAs, microRNAs (miRNAs), and messenger RNAs (mRNAs) in neonatal pig hearts. Pig heart samples collected on postnatal days 1 (P1), 3 (P3), 7 (P7) and 28 (P28) were sent for total RNA sequencing. Our data revealed a total of 7000 circRNAs in the 24 pig hearts. Pathway enrichment analysis of hallmark gene sets demonstrated that differentially expressed circRNAs are engaged in different pathways. The most significant difference was observed between P1 and the other three groups (P3, P7 and P28) in pathways related to cell cycle and muscle development. Out of the ten circRNAs that were validated through real-time quantitative polymerase chain reaction (qRT-PCR) to confirm their expression, six exhibited significant effects on cell cycle activity in human induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs) following small interfering RNA-mediated knockdown. The circRNA-miRNA-mRNA networks were constructed to understand the potential mechanisms of circRNAs in the heart. In conclusion, our study provided a dataset for exploring the roles of circRNAs in pig hearts. In addition, we identified several circRNAs that regulate cardiomyocyte cell cycle.

Research progress in endometriosis-associated ovarian cancer.

Endometriosis-associated ovarian cancer (EAOC) is a unique subtype of ovarian malignant tumor originating from endometriosis (EMS) malignant transformation, which has gradually become one of the hot topics in clinical and basic research in recent years. According to clinicopathological and epidemiological findings, precancerous lesions of ovarian clear cell carcinoma (OCCC) and ovarian endometrioid carcinoma (OEC) are considered as EMS. Given the large number of patients with endometriosis and its long time window for malignant transformation, sufficient attention should be paid to EAOC. At present, the pathogenesis of EAOC has not been clarified, no reliable biomarkers have been found in the diagnosis, and there is still a lack of basis and targets for stratified management and precise treatment in the treatment. At the same time, due to the long medical history of patients, the fast growth rate of cancer cells, and the possibility of eliminating the earliest endometriosis-associated ovarian cancer, it is difficult to find the corresponding histological evidence. As a result, few patients are finally diagnosed with EAOC, which increases the difficulty of in-depth study of EAOC. This article reviews the epidemiology, pathogenesis, risk factors, clinical diagnosis, new treatment strategies and prognosis of endometriosis-associated ovarian cancer, and prospects the future direction of basic research and clinical transformation, in order to achieve stratified management and personalized treatment of ovarian cancer patients.

A signature of seven hypoxia-related lncRNAs is a potential biomarker for predicting the prognosis of melanoma.

Melanoma is the most aggressive type of skin cancer and has a high mortality rate once metastasis occurs. Hypoxia is a universal characteristic of the microenvironment of cancer and a driver of melanoma progression. In recent years, long noncoding RNAs (lncRNAs) have attracted widespread attention in oncology research. In this study, screening was performed and revealed seven hypoxia-related lncRNAs AC008687.3, AC009495.1, AC245128.3, AL512363.1, LINC00518, LINC02416 and MCCC1-AS1 as predictive biomarkers. A predictive risk model was constructed via univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses. Patients were grouped according to the model risk score, and Kaplan-Meier analysis was performed to compare survival between groups. Functional and pathway enrichment analyses were performed to compare gene set enrichment between groups. Moreover, a nomogram was constructed with the risk score as a variable. In both the training and validation sets, patients in the low-risk group had better overall survival than did those in the high-risk group (P<0.001). The 3-, 5- and 10-year area under the curve (AUC) values for the nomogram model were 0.821, 0.795 and 0.820, respectively. Analyses of immune checkpoints, immunotherapy response, drug sensitivity, and mutation landscape were also performed. The results suggested that the low-risk group had a better response to immunotherapeutic. In addition, the nomogram can effectively predict the prognosis and immunotherapy response of melanoma patients. The signature of seven hypoxia-related lncRNAs showed great potential value as an immunotherapy response biomarker, and these lncRNAs might be treatment targets for melanoma patients.

Effectiveness of inactivated influenza vaccine against laboratory-confirmed influenza among Chinese elderly: a test-negative design.

BACKGROUND: Evidence on the effectiveness of influenza vaccination in the elderly is limited, and results are controversial. There are also few reports from China. METHODS: We conducted a test-negative case-control study design to estimate influenza vaccine effectiveness (VE) against laboratory-confirmed influenza-associated visits among elderly (aged ≥ 60 years) across four influenza seasons in Ningbo, China, from 2018 to 19 to 2021-22. Influenza-positive cases and negative controls were randomly matched in a 1:1 ratio according to age, sex, hospital, and date of influenza testing. We used logistic regression models to compare vaccination odds ratios (ORs) in cases to controls. We calculated the VE as [100% × (1-adjusted OR)] and calculated the 95% confidence interval (CI) around the estimate. RESULTS: A total of 30,630 elderly patients tested for influenza with virus nucleic acid or antigen during the study period. After exclusions, we included 1 825 influenza-positive cases and 1 825 influenza-negative controls. Overall, the adjusted VE for influenza-related visits was 63.5% (95% CI, 56.3-69.5%), but varied by season. Influenza VE was 59.8% (95% CI, 51.5-66.7%) for influenza A and 89.6% (95% CI, 77.1-95.3%) for influenza B. The VE for ages 60-69 and 70-79 was 65.2% (95% CI, 55.4-72.9%) and 69.8% (95% CI, 58.7-77.9%), respectively, but only 45.4% (95% CI, 6.2-68.2%) for ages 80 and over. CONCLUSIONS: Standard-dose inactivated influenza vaccine has shown good protection in the elderly in China. However, protection may not be satisfactory in people aged 80 years and older.

Blood Urea Nitrogen-to-Serum Albumin Ratio Predicts Fatal Outcomes in Severe Fever with Thrombocytopenia Syndrome Patients.

There are no effective therapies for severe fever with thrombocytopenia syndrome (SFTS), and existing predictors of mortality are still controversial. This retrospective study aimed to identify reliable early-stage indicators for predicting fatal outcomes in 217 patients hospitalized with an SFTS diagnosis between March 2021 and November 2023; 157 of the patients survived, and 60 died. Demographics, clinical characteristics, and laboratory parameters were reassessed in both groups. The mean age of participants was 64.0 (interquartile range: 54.5-71.0) years, and 42.4% (92/217) were males. Based on a multivariate Cox regression analysis, the blood urea nitrogen-to-serum albumin ratio (BAR) (hazard ratio [HR]:4.751; 95% CI: 2.208-10.226; P <0.001), procalcitonin level (HR: 1.946; 95% CI: 1.080-3.507; P = 0.027), and central nervous system symptoms (HR: 3.257; 95% CI, 1.628-6.513; P = 0.001) were independent risk factors for mortality in SFTS patients. According to a receiver operating characteristic curve analysis, a BAR with an area under the curve of 0.913 (95% CI: 0.873-0.953; P <0.001), a sensitivity of 76.7%, and a specificity of 90.4% showed better predictive performance for fatal outcomes than other classical indicators reported. The Kaplan-Meier survival curve confirmed that an increased BAR was linked with an unfavorable prognosis in SFTS patients (P <0.001 by log-rank test). In conclusion, the results indicate that high BAR levels are markedly related to substandard outcomes and are a reliable and readily accessible predictor of fatal outcomes in SFTS patients.

Correction: Zhao et al. Hypermethylation of UCHL1 Promotes Metastasis of Nasopharyngeal Carcinoma by Suppressing Degradation of Cortactin (CTTN). Cells 2020, 9, 559.

In the original publication [...].

Repeated vaccination does not appear to significantly weaken the protective effect of influenza vaccine in the elderly: A test-negative case-control study in China.

BACKGROUND: The impact of repeated influenza vaccination on vaccine effectiveness has been a topic of debate. Conducting more multinational, multicenter studies in different influenza seasons is crucial for a better understanding of this issue. There is a lack of comprehensive related research reports in China. METHODS: Using the Regional Health Information Platform, we conducted a test-negative case-control study to evaluate the impact of repeated vaccination on the prevention of laboratory-confirmed influenza in individuals aged 60 and above in Ningbo during four influenza seasons from 2018-19 to 2021-22. Influenza-positive cases and negative controls were matched in a 1:1 ratio based on the visiting hospital and the date of influenza testing. Propensity score adjustment and multivariable logistic regression were used to estimate risk and address confounding effects. RESULTS: During the study period, a total of 30,630 elderly patients underwent influenza virus nucleic acid or antigen testing. After exclusions, we included 1976 cases of influenza-positive and 1976 cases of influenza-negative controls. Multivariable logistic regression analysis revealed that individuals receiving the vaccine in two consecutive seasons did not exhibit a significantly increased risk of influenza illness compared to those receiving the vaccine only in the current season (adjusted odds ratio: 1.22, 95% confidence interval: 0.94-1.58). However, the risk of influenza illness was found to be elevated in individuals who received the vaccine only in the previous season (adjusted odds ratio: 1.56, 95% confidence interval: 1.15-2.10) and even further elevated in those who had not received the vaccine in either of the consecutive two seasons (adjusted odds ratio: 3.39, 95% confidence interval: 2.80-4.09). CONCLUSIONS: Regardless of the vaccination history in the previous season, receiving the current season influenza vaccine is the best choice for the elderly population. Our study supports the initiative to vaccinate elderly individuals against influenza annually.