Hepatocellular carcinoma (HCC), the most frequent type of liver cancer, is a major source of cancer-related morbidity and mortality worldwide. B7-H6 is overexpressed in a variety of cancers including HCC and plays a key role in tumor biology and augments hepatoma cell proliferation, invasion, migration and cell-cycle progression. So, in this investigation we examined the role of B7-H6 silencing by specific siRNA in HepG2 cell line together with Paclitaxel treatment to reveal the potency of combining efficient targeted therapy with chemotherapy against tumor.

HepG2 cells were transfected with B7-H6-siRNA by the electroporation method, then treated with an appropriate dose of Paclitaxel determined by MTT. The consequence of B7-H6-siRNA transfection, Paclitaxel treatment and their simultaneous usage on the apoptosis, cell cycle and migration of HepG2 cells was evaluated by flow cytometry and wound-healing assay. Furthermore, the expression levels of Bax, Bcl-2, MMP9, B-Catenin, C-Myc and Cyclin D1 were also examined by quantitative real-time PCR.

Paclitaxel treated cells and B7-H6 suppressed cells and cells that received both of them became more sensitive to apoptosis and cell cycle arrest at the G2 phase and they showed reduced ability to migrate. Also, this therapeutic strategy had potency in reduction of BCL-2 as an anti-apoptotic gene and exaggeration of the apoptosis-involved gene Bax expression and reduction of other tumor associated genes' expression including MMP-9, B-Catenin, C-Myc and Cyclin D1.

These findings further support that Paclitaxel therapy in conjunction with B7-H6 suppression may present a potential option for successful cancer treatment.

This article provides updated global cancer statistics for the year 2024 based on the GLOBOCAN estimates of the International Agency for Research on Cancer. The authors describe national cancer incidence and mortality by world region and the Human Development Index and predict the burden in 2050 based on demographic trends. In 2024, an estimated 20.6 million new cancer cases (19.5 million excluding nonmelanoma skin cancer) and 9.8 million deaths (9.7 million excluding nonmelanoma skin cancer) occurred worldwide, equivalent to one in five people developing cancer during their lifetime and one in nine men and one in 13 women dying from the disease. Lung cancer is the most frequently diagnosed cancer, responsible for almost 2.6 million new cases (12.8%), followed by female breast (11.8%), colorectal (9.9%), prostate (7.5%), and stomach (4.7%) cancer. Lung cancer is also the leading cause of cancer death, with an estimated 1.9 million deaths (19.1%), followed by colorectal (9.4%), liver (7.5%), female breast (7.1%), and stomach (6.6%) cancer. Incidence rates vary four- to five-fold across regions, with the highest rates found in Australia/New Zealand (men, 477 per 100,000; women, 396 per 100,000), whereas mortality rates differ two-fold, with elevated rates in Eastern Europe for men (158 per 100,000) and Melanesia for women (108 per 100,000). The incidence burden is predicted to reach 34.4 million by 2050, up 67% from 2024, with the largest proportional increases in lower Human Development Index countries. Although global variation in cancer profiles demands a nuanced approach to cancer control at national and regional levels, primary prevention must be at the forefront, including intensified efforts to reduce tobacco use, prevent infections, lower alcohol consumption and excess body weight, and increase physical activity.

Ganoderic acid DM (GA-DM), a triterpenoid derived from Ganoderma lucidum, exhibits anti-cancer and anti-diabetic activities, but the underlying mechanisms of action remain unclear. To identify genetic modulators of the GA-DM response, we conducted a genome-wide CRISPR/Cas9 knockout screen in human melanoma cells. The screen revealed key roles for genes regulating lipid metabolism and inflammatory signalling, particularly those involved in the SREBP (sterol regulatory element-binding protein) and NF-jB (nuclear factor kappa-light-chain-enhancer of activated B cells) pathways, in the cellular response to GA-DM. While loss of genes involved in the regulation of cholesterol biosynthesis conferred resistance to GA-DM, disruption of genes involved in ubiquitin-mediated proteolysis and the Hippo pathway sensitised cells to GA-DM. Inflammatory genes enriched at later time points suggests that a delayed cellular response contributes to cytotoxicity. Our findings propose a mechanistic model wherein GA-DM perturbs lipid and inflammatory pathways to exert cytotoxic effects and highlight potential targets to enhance its therapeutic efficacy. This work demonstrates the utility of functional genomics in elucidating the mechanisms of action of natural products and guiding rational drug development.

Mycoplasma pneumoniae pneumonia (MPP) exhibits significant clinical heterogeneity in children. This study investigated the clinical utility of serum interleukin-6 (IL-6), interleukin-8 (IL-8), and the T helper/T suppressor (Th/Ts) cell ratio for evaluating disease severity and 1-month short-term clinical outcomes in pediatric MPP. We retrospectively enrolled 194 hospitalized children with MPP without co-infection (102 mild, 92 severe; 171 favorable short-term clinical outcome, 23 poor short-term clinical outcome). Core biomarker levels were compared between groups. Diagnostic performance was evaluated using receiver operating characteristic (ROC) curves. Bootstrap mediation analysis was used to explore the statistical association pathway between systemic inflammation and cellular immune status. For short-term outcome risk stratification, LASSO logistic regression was performed as a sensitivity analysis, and candidate prognostic models were compared. Patients with severe MPP and poor short-term clinical outcomes exhibited significantly elevated IL-6 and IL-8 levels and a reduced Th/Ts ratio (all P < 0.001). A combined diagnostic model incorporating these three biomarkers achieved an AUC of 0.943 for predicting severe MPP. Mediation analysis suggested that the Th/Ts ratio partially mediated the associations of IL-6 (30.3%) and IL-8 (19.2%) with disease severity. For short-term outcome risk stratification, a parsimonious exploratory nomogram incorporating lactate dehydrogenase (LDH), IL-6, and the Th/Ts ratio showed favorable internal performance (C-index = 0.89), calibration, and clinical net benefit.Conclusions: Pediatric MPP is characterized by an inflammation-immune imbalance pattern involving elevated IL-6 and IL-8 levels and a reduced Th/Ts ratio. The LDH, IL-6, and Th/Ts ratio-based nomogram may serve as an exploratory risk-stratification tool for 1-month short-term clinical outcomes, but external validation in multicenter prospective cohorts is required before routine clinical application.

To investigate the association between ventilator-associated pneumonia and outcomes in mechanically ventilated nontraumatic intracerebral hemorrhage patients.

Retrospective data analysis from the National Inpatient Sample database, including patients from 2008 to 2022, for adult hospitalized intracerebral hemorrhage patients on mechanical ventilation. Variables included age, sex, race, hospital location, comorbidities, indicators of intracerebral hemorrhage severity, and neurosurgical procedures. The cohort was divided into ventilator-associated pneumonia and non-ventilator-associated pneumonia groups. Propensity-score matching was applied to balance comorbidities and severity between the two groups. Binary logistic regression was used to analyze the predetermined outcomes. P value was set at 0.05.

Of 70,870 mechanically ventilated intracerebral hemorrhage patients, 3,183 (4.5%) developed ventilator-associated pneumonia. Intracerebral hemorrhage patients with ventilator-associated pneumonia were younger (59 [49 - 69] versus 65 [54 - 76]), more frequently male (62.3% versus 54.3%), and more frequently black (27.4% versus 21.2%), p < 0.001 for all. Ventilator-associated pneumonia patients had a higher rate of cerebral edema (50.7% versus 37%), brain compression (32.5% versus 27.3%), obstructive hydrocephalus (36.1% versus 24.7%), and neurosurgical procedures, both external ventricular drain (38.2% versus 20.2%) and hematoma evacuation (13.8% versus 8.6%), p < 0.001 for all. Time from presentation to intubation was longer in ventilator-associated pneumonia (days; 0 [0 - 3] versus 0 [0 - 1], p < 0.001). After 1:1 propensity-score matching, binary logistic regression revealed that ventilator-associated pneumonia remained independently associated with prolonged length of hospital stay (OR = 1.56, 95%CI 1.3 - 1.82; p < 0.01), higher hospitalization cost (OR = 1.47, 95%CI 1.26 - 1.7; p < 0.01) and higher odds of unfavorable discharge disposition (OR = 1.26, 95%CI 1.06 - 1.49; p = 0.01).

Ventilator-associated pneumonia significantly complicates the care of mechanically ventilated intracerebral hemorrhage patients, increasing the healthcare resource utilization, prolonging length of stay, and being associated with worse short-term functional outcomes.

 Nursing students face significant academic and clinical stressors that can affect their psychological well-being. These challenges are intensified during extraordinary events, such as the coronavirus disease 2019 (COVID-19) pandemic.

 This study investigated psychological distress and resilience among junior (1st year - 2nd year) and senior (3rd year - 4th year) undergraduate nursing students exposed to a major stressor at two universities in the Western Cape, South Africa.

 A survey was conducted among 589 nursing students during and after COVID-19. Most respondents were female (77.4%) and junior students (75.2%), with a mean age of 22.5 years (± 4.6). Data collection took place at University A (February 2021-March 2021) and University B (November 2021-February 2022). Measures include psychological distress (Kessler-10), resilience (Response to Stressful Experiences Scale) and fear of COVID-19 (Fear of COVID-19 Scale).

 Overall, students reported mild psychological distress and fear of COVID-19, and high levels of resilience. Senior students experienced significantly higher psychological distress than juniors (p  0.001), but lower fear of COVID-19 (p = 0.028). Resilience did not differ significantly between groups, with most students demonstrating high resilience.

 Nursing students showed strong resilience despite the added pandemic-related stressors. Elevated distress among seniors, however, highlights the need for targeted psychological support. Strengthening resilience within nursing education may prepare students to manage future crises and contribute to a sustainable, adaptable nursing workforce.Contribution: This study provides evidence on the psychological well-being of nursing students in South Africa during the COVID-19 pandemic. It emphasises the importance of resilience-building interventions within nursing curricula and institutional support systems to safeguard student health and professional readiness.

 Tuberculosis (TB) has remained a significant public health challenge for many years. Individuals with weakened immune systems because of other illnesses are particularly vulnerable to contracting TB. In March 2020, South Africa implemented a disease control strategy which ceased and disrupted daily routines, including healthcare services delivery. The study aimed to determine and describe the impact of coronavirus disease 2019 (COVID-19) lockdown restrictions on the utilisation of TB services, pre-COVID-19 and peri-COVID-19.

 A cross-sectional retrospective study using National Institute for Communicable Diseases (NICD) and National Department of Health (NDoH) data from Johannesburg, South Africa, was conducted to assess COVID-19 restrictions' impact on TB service use from January 2018 to December 2021, examining trends across periods and influencing factors. The study included individuals who sought TB services, showed TB symptoms, or tested positive or negative for TB during the study period.

 The secondary data collected included children ( 10 years old), young adolescents (10-14 years old), older adolescents (15-19 years old), young adults (20-24 years old), adults (25-49 years old) and older adults (≥ 50 years old). Tuberculosis service use was highest among adult females aged 25-29 years old (51.3%) and lowest among females ≥ 50 years old (32.6%).

 A marked decline in TB service use was observed during the peri-COVID-19 period. Results demonstrated that COVID-19 restrictions caused a substantial and sustained decline in TB service utilisation in Johannesburg, even when accounting for broader determinants of care-seeking.Contributions: This study provides valuable insight into the impact of COVID-19 restrictions on TB service utilisation and highlights the broader societal effects of a pandemic.

The reported prevalence of secondary traumatic stress (STS) among nurses varies considerably across studies, ranging from 22. 1 to 84.4%. This meta-analysis aimed to estimate the pooled prevalence of STS and identify potential moderating factors among nurses.

From the inception of each target database to April 2026, a comprehensive search was performed across PubMed, Web of Science, Scopus, Embase, Cochrane Library, CINAHL, and PsycINFO. We calculated the pooled prevalence of STS using a random-effects model and assessed heterogeneity using the I² statistic. Subgroup analyses and meta-regression were conducted to explore potential sources of heterogeneity.

A total of 28 studies comprising 7,090 nurses were included. The pooled prevalence of STS in nurses was 57.3% (95% CI: 49.7-64.9%). STS prevalence was significantly associated with mean age (β = -0.064, p = 0.023), work experience (β = -0.080, p = 0.040), publication year (during COVID-19: β = 0.979, p = 0.024; after COVID-19: β = 0.848, p = 0.030), and geographic region (North America: β = -0.881, p = 0.019; Europe: β = -1.031, p = 0.005).

Our findings indicated that STS was very prevalent in nurses, and the prevalence is moderated by mean age, work experience, publication year, and geographic region. Regular STS assessments and multi-level support systems, such as early warning, peer support, and mental health training, are recommended to reduce STS risk and enhance the wellbeing of nurses.

More than six years after the emergence of COVID-19, Japan continues to experience persistently elevated excess mortality despite entering a post-pandemic phase. Excess mortality, defined as the difference between observed and expected deaths, reflects both direct and indirect effects of the pandemic, including healthcare disruption, delayed care, and broader social changes. In Japan, mortality decreased slightly in 2020 but increased markedly from 2022 onward, with annual excess deaths approaching 100,000, despite widespread vaccination and the predominance of the less virulent Omicron variant. Multiple factors may underlie this sustained increase, including population aging, changes in healthcare access, delayed diagnosis and treatment, regional disparities, and psychosocial stress. Some ecological and observational studies have reported a statistical association between repeated COVID-19 booster vaccination and excess mortality in Japan; however, these findings do not establish causality, and a causal relationship cannot currently be concluded. Against this background, this narrative review examines persistent excess mortality in Japan, uses the literature on repeated booster vaccination as an illustrative example to highlight methodological limitations, and discusses the need for nationwide, linked individual-level data infrastructure and appropriate analytical frameworks for more robust future evaluations.

BACKGROUNDThere are no known serum biomarkers that provide mechanistic insight or prognostic enrichment for post-COVID-19 pulmonary fibrosis.METHODSWe tested associations of serum biomarkers with radiographic fibrosis-like abnormalities (reticulation, traction bronchiectasis, or honeycombing) on thoracic computed tomography (CT) scans 4 months, 15 months, and 3 years after hospitalization in an American discovery cohort of severe-to-critical COVID-19 survivors, and externally validated findings in 2 Canadian cohorts of moderate-to-critical COVID-19 survivors. In the discovery cohort, we investigated the dose-response relationship of the biomarker with CT-derived airway-to-lung ratio. We performed single-cell RNA sequencing (scRNA-seq) of transbronchial lung biopsies from COVID-19 survivors obtained 3 years after COVID-19 hospitalization and conducted immunofluorescence analysis of COVID-19 lung explants.RESULTSAmong 150 discovery cohort participants, only higher levels of circulating club cell secretory protein-16 (CC16, encoded by the SCGB1A1 gene) at hospital discharge, 4 months, 15 months, and 3 years were associated with thoracic CT fibrosis-like abnormalities in cross-sectional and longitudinal analyses. Higher CC16 levels were associated with thoracic CT fibrosis-like abnormalities in 2 validation cohorts (n = 56 and n = 37). CC16 levels were linearly associated with increased airway-to-lung ratio. scRNA-seq revealed increased proportions of epithelial cells expressing SCGB1A1 and SCGB1A1/MUC5B in COVID-19 survivors with fibrosis. Immunofluorescence analysis of COVID-19 lung explants demonstrated increased numbers of SCGB1A1-expressing epithelial cells only in small (<100 μm) airways, with 3-fold more CC16/MUC5B-coexpressing cells in respiratory bronchioles..CONCLUSION. Higher CC16 levels are associated with CT fibrosis-like abnormalities for up to 3 years following moderate-to-critical COVID-19. Increased CC16 reflects dysregulated small airway epithelial progenitor cell remodeling and increased expansion of CC16+MUC5B+ epithelial cells in respiratory bronchioles after COVID-19.TRIAL REGISTRATIONNot applicable.FUNDINGDepartment of Defense, NIH, and Japan Society for the Promotion of Science for Young Scientists.