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Knockdown of LINC00853 Inhibits the Progression and Immune Escape of Hepatocellular Carcinoma by Targeting the miR-16-5p/PD-L1 Axis.3 days agoLong non-coding RNAs (lncRNAs) play crucial roles in hepatocellular carcinoma (HCC), offering valuable insights for therapeutic development. However, the clinical significance and functional mechanisms of LINC00853 in HCC remain poorly understood. This study aimed to evaluate the prognostic value of LINC00853 in HCC patients, and to investigate its underlying mechanisms in regulating HCC. A cohort of 123 HCC patients was enrolled in this study. LINC00853 expression in tumor tissues was quantified by quantitative reverse transcription-PCR (qRT-PCR). Prognostic significance of LINC00853 was assessed using Kaplan-Meier curves and Cox regression models. In vitro functional assays, including Cell Counting Kit-8 (CCK-8) and Transwell assays, were conducted to evaluate the effects of LINC00853 knockdown on cell proliferation, migration, and invasion. The regulatory axis involving LINC00853, miR-16-5p, and programmed death-ligand 1 (PD-L1) was validated by dual-luciferase reporter assays. The role of LINC00853 in immune escape was investigated by co-culturing CD8+ T cells with HCC cells and measuring cytotoxic activity along with cytokine (TNF-α, IFN-γ, IL-10, and TGF-β) levels. LINC00853 was significantly overexpressed in HCC tissues and was associated with unfavorable prognosis. Silencing LINC00853 suppressed the proliferation, migration, and invasion of HCC cells. Mechanistically, LINC00853 functioned as a molecular sponge for miR-16-5p, thereby upregulating PD-L1 expression. In the co-culture system, LINC00853 knockdown enhanced CD8+ T cell cytotoxicity and promoted the secretion of inflammatory cytokines (TNF-α and IFN-γ), while reducing immunosuppressive factors (IL-10 and TGF-β). These effects were reversed by the miR-16-5p inhibitor. LINC00853 may serve as a novel prognostic marker for HCC. Knockdown of LINC00853 suppresses the progression and immune escape by targeting the miR-16-5p/PD-L1 axis, suggesting its potential as a therapeutic target.CancerCare/ManagementPolicy
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Clinicopathological profile of high-grade differentiated thyroid carcinoma in Indonesian tertiary hospital.3 days agoHigh-grade differentiated thyroid carcinoma (HGDTC) is a recently recognized entity in the 2022 World Health Organization classification, representing a more aggressive subtype of differentiated thyroid carcinoma. Previously, high-grade features such as increased mitotic activity and tumor necrosis were often overlooked, despite being important independent prognostic factors. Although rare, HGDTC carries significant diagnostic, prognostic, and therapeutic implications. Data remain limited in Indonesia.
This retrospective descriptive study reviewed 565 thyroid carcinoma cases diagnosed at Cipto Mangunkusumo Hospital from 2019 to 2024. Eleven cases (1.9%) met HGDTC criteria. Clinicopathological characteristics, histologic subtypes, Ki-67 proliferation index, molecular alterations, treatment modalities, and clinical outcomes were analyzed.
Patients had a mean age of 54.6 years, with a female-to-male ratio of 2.7:1. Papillary thyroid carcinoma was the main type (90.9%), with the tall cell subtype predominating. Mean tumor size was 6.4 cm. Lymphatic invasion, vascular invasion, and extrathyroidal extension were present in 54.5%, 18.2%, and 45.5% of cases, respectively. All tumors showed necrosis. Mean mitotic count was 3 per 2 mm². The Ki-67 index ranged from 5% to 45% (median, 14%). BRAFV600E and TERT promoter mutations were detected in 18.2% and 36.4% of cases, respectively, with co-mutations in 18.2%. Six cases (54.5%) had metastases at time of diagnosis. During a mean follow-up of 20.5 months, one patient (9.1%) developed new vertebral metastases and all patients (100%) remained alive.
HGDTC presents with more aggressive characteristics and a worse prognosis. Accurate diagnosis, molecular profiling, and long-term monitoring are essential for optimal management.CancerCare/Management -
A novel mutation of IFT140 in a preschool child with Mainzer-Saldino syndrome accompanied by rare tumor blastic plasmacytoid dendritic cell neoplasm: a case report.3 days agoMainzer-Saldino syndrome is a rare autosomal recessive ciliopathy characterized by cone-shaped epiphyses, chronic renal failure, and early-onset severe retinal dystrophy. Blastic plasmacytoid dendritic cell neoplasm is a rare hematologic malignancy. However, the association between these two diseases is unclear, and the coincidence of the two diseases has not been previously reported.
We report a 5-year-5-month-old Chinese boy who experienced conical epiphysis, retinitis pigmentosa, and distinct cutaneous lesions. Renal ultrasound indicated morphological changes in the kidney. The whole exon sequencing revealed that the proband harbored compound heterozygous variants, including a novel variant c.2471T > C (p.Leu824Pro), a maternally inherited missense variant, and c.1990G > A (p.Glu664Lys) inherited from his father in the IFT140 gene. The proband was clinically and molecularly diagnosed as Mainzer-Saldino syndrome. Meanwhile, the diagnosis as blastic plasmacytoid dendritic cell neoplas (BPDCN) was confirmed by the biopsy of skin mass.
This is the first case of Mainzer-Saldino syndrome combined with a rare tumor blastic plasmacytoid dendritic-cell neoplasm. Our research expands the mutation spectrum of the IFT140 gene, helping to refine the phenotypic diversity of Mainzer-Saldino syndrome.CancerCare/Management -
Helicobacter pylori activates histone lactylation to promote gastric cancer progression and immune evasion through the HAS2/c-MYC/PD-L1 axis.3 days agoMetabolic reprogramming and epigenetic alterations play important roles in driving tumor microenvironment (TME) remodeling and immune evasion in gastric cancer (GC). Histone lactylation links glycolytic metabolism to transcriptional regulation, but its role in Helicobacter pylori (H. pylori)-associated GC progression remains largely elusive.
Multiomics analysis (ChIP-seq and RNA-seq) with in vitro GC/CD8+ T-cell coculture systems and in vivo mouse xenograft models were employed in this study. Clinical GC tissue cohorts were analyzed to validate the clinical relevance of the identified signaling pathways. The epigenetic and immunological impacts of lactate metabolism were assessed using glycolysis inhibitors (2-DG and oxamate) and genetic silencing of LDHA and LDHB.
Histone lactylation, specifically H3K18la, was significantly elevated in GC tissues and further elevated upon H. pylori infection. Pharmacological inhibition of glycolysis or LDHA/B double knockdown (DKD) markedly reduced H3K18la levels, suppressed GC cell proliferation, and restored CD8+ T cell-mediated cytotoxicity. Mechanistically, H3K18la directly bound to the HAS2 promoter, transcriptionally activating its expression. Upregulated HAS2 facilitated the nuclear translocation of c-MYC, which subsequently bound to the CD274 promoter to induce PD-L1 expression. Furthermore, c-MYC overexpression rescued PD-L1 levels and reversed the restored CD8+ T-cell cytotoxicity in LDHA/B-deficient GC cells. In vivo, the combination of oxamate and anti-PD-1 blockade synergistically enhanced CD8+ T-cell infiltration and exerted robust antitumor efficacy.
H. pylori-associated lactate-driven H3K18la promotes GC progression and immune evasion through the HAS2/c-MYC/PD-L1 axis. These findings provide preclinical support for combining metabolic inhibition with PD-1 blockade in GC, particularly in H. pylori-associated disease.CancerCare/ManagementPolicy -
Pancreatic Adenosquamous Carcinoma with Direct Gastric Invasion:Preoperative Diagnosis by Endoscopic Biopsy -A Case Report.3 days agoPancreatic adenosquamous carcinoma (PASC) is a rare and highly aggressive subtype of pancreatic cancer with a dismal prognosis, and its preoperative diagnosis remains challenging. We report the case of an 82-year-old man who presented with epigastric pain and appetite loss. Imaging studies revealed a large, partially necrotic mass in the tail of the pancreas that was contiguous with the posterior gastric wall, accompanied by multiple metastases to the liver, lungs, regional lymph nodes, and peritoneum. Upper gastrointestinal endoscopy identified a large, excavated ulcer within a submucosal tumor-like elevation, and biopsies from the ulcer margin confirmed the presence of squamous cell carcinoma. The pathological findings showed PASC. The patient was diagnosed with Stage Ⅳ PASC, and palliative care was selected in view of advanced dementia and disease extent. This case shows that PASC can present with direct gastric penetration, and it highlights the value of direct endoscopic biopsy of the invaded gastric site to secure a definitive preoperative histopathologic diagnosis. PASC should be considered in the differential diagnosis of pancreatic masses that exhibit gastric invasion and marked internal necrosis on imaging. J. Med. Invest. 73 : 286-290, February, 2026.CancerCare/Management
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[Translated article] Injury incidence, burden, and patterns in Peruvian football: A retrospective analysis of the 2023 regular season versus the 2020 season during the COVID-19 pandemic.3 days agoThe COVID-19 pandemic led to the suspension of football leagues worldwide, resulting in changes to tournament formats and player performance. While European leagues have reported injury characteristics during this period, similar analyses are lacking in South America. This study aimed to compare injury incidence, burden, and patterns between a regular season (2023) and the pandemic-affected season (2020) in Peruvian professional football.
A total of 266 and 360 official matches were analyzed from the 2020 and 2023 seasons, respectively. Injury data were collected through video analysis of official broadcasts, sports media publications, and official statements from club medical departments. Injury severity was classified based on days absent until return to full competition. Injury burden was defined as total days absent per 1000h of exposure. Injury incidence rates (injuries per 1000h) and injury characteristics (type, anatomical location, mechanism, and severity) were compared between seasons.
The 2020 season included 19 teams, 521 registered players, and 28 matches per team. In 2023, 20 teams and 532 players participated, with each team playing 37 matches. No significant difference was found in match injury incidence between seasons. However, injury burden in 2020 was 1.23 times higher (95% CI, p<.01) compared to 2023, with a median difference of 6 days absent per injury (U=77, p<.001). Contact injuries significantly decreased in the 2020 season (RR 0.58, 95% CI, p<.05).
Although injury incidence remained similar, the 2020 pandemic season showed higher injury burden and fewer contact injuries, highlighting the need for adaptive strategies to protect athlete health during unexpected interruptions.Chronic respiratory diseaseAccessAdvocacy -
Injury incidence, burden, and patterns in peruvian football: A retrospective analysis of the 2023 regular season versus the 2020 season during the COVID-19 pandemic.3 days agoThe COVID-19 pandemic led to the suspension of football leagues worldwide, resulting in changes to tournament formats and player performance. While European leagues have reported injury characteristics during this period, similar analyses are lacking in South America. This study aimed to compare injury incidence, burden, and patterns between a regular season (2023) and the pandemic-affected season (2020) in Peruvian professional football.
A total of 266 and 360 official matches were analyzed from the 2020 and 2023 seasons, respectively. Injury data were collected through video analysis of official broadcasts, sports media publications, and official statements from club medical departments. Injury severity was classified based on days lost until return to full competition. Injury burden was defined as total days lost per 1000hours of exposure. Injury incidence rates (injuries per 1000hours) and injury characteristics (type, anatomical location, mechanism, and severity) were compared between seasons.
The 2020 season included 19 teams, 521 registered players, and 28 matches per team. In 2023, 20 teams and 532 players participated, with each team playing 37 matches. No significant difference was found in match injury incidence between seasons. However, injury burden in 2020 was 1.23 times higher (95% CI, P<.01) compared to 2023, with a median difference of 6 days lost per injury (U=77, P<.001). Contact injuries significantly decreased in the 2020 season (RR 0.58, 95% CI, P<.05).
Although injury incidence remained similar, the 2020 pandemic season showed higher injury burden and fewer contact injuries, highlighting the need for adaptive strategies to protect athlete health during unexpected interruptions.Chronic respiratory diseaseAccessAdvocacy -
Burnout and Adverse Childhood Experiences in the Maternal and Child Health Workforce.3 days agoBurnout has risen sharply since the COVID-19 pandemic, especially in healthcare. Emerging evidence suggests adverse childhood experiences (ACEs) may increase burnout risk. This study examined the relationship between burnout and ACEs within the maternal and child health (MCH) workforce and assessed ACE prevalence.
An anonymous cross-sectional survey of MCH clinicians (n = 477) was administered via Qualtrics. Eligibility included being ≥18 years old, working in the MCH workforce, and practicing ≥1 year. Burnout was assessed using the Maslach Burnout Inventory-Human Services Survey (MBI-HSS). ACEs were measured using the ACE questionnaire with minor wording modification. ANOVA and linear regression were used to evaluate associations between ACE exposure and burnout.
Over half (57%) reported ≥1 ACE; 31% reported ≥4. Burnout levels were high (Personal Accomplishment = 26.47 ± 8.94; Emotional Exhaustion = 32.98 ± 8.56; and Depersonalization = 15.62 ± 5.82). Participants with ≥4 ACEs had significantly higher emotional exhaustion and lower personal accomplishment. Those with 1 to 2 ACEs had lower emotional exhaustion and depersonalization than those with zero ACEs.
The MCH workforce shows a high prevalence of ACEs and elevated burnout. A dose-response relationship was observed, with ≥4 ACEs associated with greater burnout. However, lower burnout among those with 1 to 2 ACEs suggests possible resilience pathways. Workforce programs should account for early life adversity and integrate resilience-informed approaches.Chronic respiratory diseaseAccessAdvocacy -
Influenza infection influencing factors and direct economic burden - A study based on hospitalized cases of severe acute respiratory infection (SARI).3 days agoInfluenza viruses are one of the key pathogens causing acute respiratory infections in humans, which lead to significant economic burdens. From August 2023 to May 2024, hospitalized SARI cases were recruited from Shouguang People's Hospital in Weifang, Shandong Province. Reverse Transcription-Polymerase Chain Reaction was used to detect influenza virus nucleic acids, including influenza A and B viruses. Meanwhile, clinical information and detailed expense bills of these hospitalized SARI cases were collected to conduct analyses on demographics and clinical characteristics. In addition, cost analysis and investigation of factors influencing the economic burden of influenza were carried out from the perspectives of third-party payers and society. A total of 1,772 SARI cases were included in the study, with an influenza positivity rate of 7.5%. Among these cases, the proportion of hospitalized patients aged 70 y and above was the highest. Influenza viruses were more likely to result in severe illness or death, while influenza vaccination could significantly reduce the influenza positivity rate. The total medical insurance expenditure was $65,844.62, accounting for 64.3% of the total economic burden. For influenza-positive cases, the average direct medical burden was $783.95 per person, and the average out-of-pocket expenditure per patient was $288.88. Among the costs, laboratory testing fees and medication treatment fees accounted for the highest proportions. The study found that age, length of hospital stay, and vaccination status were factors influencing the direct medical economic burden of influenza. Influenza vaccination was significantly associated with the influenza positivity rate.Chronic respiratory diseaseAccessCare/ManagementAdvocacy
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What Gave Us Strength: Perspectives From Aboriginal Community Controlled Health Services Staff on Working During the COVID-19 Pandemic.3 days agoThere is limited evidence on the social and emotional wellbeing (SEWB) needs of staff working at Aboriginal Community Controlled Health Services (ACCHS) in Australia. The current study employed qualitative research methods to explore ACCHS staff's experience during the COVID-19 pandemic and its impact on their SEWB, and to identify factors that provided strength.
Yarning Circles and one-on-one Yarns were employed to explore clinical and non-clinical ACCHS staff's experiences. Participants included staff who identified as Aboriginal and/or Torres Strait Islander, or were non-Indigenous. Thirty-one staff from 5 ACCHSs participated in 7 Yarning Circles and 3 one-on-one Yarns, between December 2021 and June 2022. Staff shared their perspectives on (i) ACCHSs' responses, (ii) community and staff reaction, and (iii) impact of service-level changes on their SEWB. Data was analysed using thematic analysis.
The main themes identified as impacting ACCHS staff's SEWB were: (1) constant change and prolonged stress, (2) community as a source of strength, (3) leadership safeguarding community and staff, (4) pride in their response, and (5) opportunities to lessen psychological toll. Staff were motivated by the seamlessness of their roles. They were motivated by positive work environment, reliable infection control measures, and resourceful leadership. Major concerns included fear of contracting and transmitting infection, and long-term consequences of disrupted patient care. There was a lack of awareness among staff about formal SEWB support, and if aware they were hesitant to use services due to cultural safety and privacy concerns. A major source of support for ACCHS staff was peer support.
During the COVID-19 pandemic ACCHS staff experienced prolonged stress exacerbated by constant changes, inconsistent information, misinformation, and lack of resources. Staff found strength in community, cultural connections, and management's response. Informal peer support was important in upholding ACCHS staff's SEWB, suggesting that structured peer support can provide ongoing support.Chronic respiratory diseaseAccessCare/ManagementAdvocacy