Abstrast Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy associated with a poor prognosis and considerable resistance to conventional therapies. While radical surgery may offer benefit for a subset of patients with early-stage disease, recent decades have witnessed notable progress in immunotherapy, yielding encouraging outcomes across both hematologic cancers and solid tumors in preclinical and clinical settings. Despite these advances, PDAC remains largely refractory to current immunotherapeutic strategies, owing largely to its unique tumor microenvironment (TME). The TME plays a pivotal role in modulating tumor progression, metastatic dissemination, and treatment response. It is commonly marked by a profoundly immunosuppressive milieu that attenuates effective anti-tumor immunity and complicates therapeutic intervention. The complex cellular and molecular composition of the TME poses significant challenges for the development of novel treatment modalities. Consequently, there is a growing imperative to therapeutically “reprogram” various components and functions within the TME to improve clinical outcomes in PDAC patients. This review seeks to elucidate how the PDAC TME and its key immunosuppressive constituents influence disease progression and response to immunotherapy. A deeper understanding of these interactions may open avenues for innovative treatment approaches capable of overcoming the barriers imposed by the TME in pancreatic cancer.

Abstract Objectives This study provides the first comprehensive assessment of the global thyroid cancer burden from 1990 to 2021, focusing on incidence, mortality, and DALYs trends across 204 countries. Methods Using Global Burden of Disease (GBD) 2021 data, age-standardized rates (ASRs) and estimated annual percentage changes (EAPCs) were calculated. Associations with the Socio-demographic Index (SDI) were analyzed via linear regression. Results Globally, the age-standardized incidence rate increased from 2.06 to 2.91 per 100,000 (EAPC=1.25), with women accounting for 67 % of cases. Mortality showed a modest decline (EAPC=−0.23), but DALYs remained high (14.57 million in 2021). High-SDI regions, such as North America, accounted for 72 % of cases, reflecting intensive screening, whereas low-SDI regions, particularly Sub-Saharan Africa, contributed 68 % of deaths due to delayed diagnosis. High BMI contributed 1.68 % of DALYs, peaking at 4.26 % in Andean Latin America. Incidence varied significantly across countries, from 7.13 per 100,000 in Saudi Arabia (linked to iodine excess) to 0.014 per 100,000 in Tajikistan (iodine deficiency). Mortality was highest among elderly males, reaching 12.57 per 100,000 in those aged ≥90 years. Conclusions The rising global burden of thyroid cancer highlights pronounced gender and regional disparities. High-SDI regions should prioritize risk-stratified strategies to reduce overdiagnosis, while low-SDI regions require improved access to healthcare. Targeted efforts in early detection and metabolic risk reduction are critical to mitigate disease burden.

Abstract Objectives This study aimed to evaluate the significance of integrating hearing screening with genetic testing for hereditary deafness. Methods A retrospective analysis was performed on the hearing screening and genetic testing outcomes of 10,754 newborns delivered at Hangzhou Women’s Hospital from June 2020 to December 2022. Hearing evaluations were conducted using transiently evoked otoacoustic emissions (TEOAE) and automated auditory brainstem response (AABR). For genetic testing, dried blood spots were collected, and 15 variants across four genes (GJB2, GJB3, SLC26A4, and mtDNA 12S rRNA) were examined using a DNA microarray platform. Results Among the 10,754 infants, the most commonly detected mutations were GJB2c.235delC (47.26 %) and SLC26A4 IVS7-2 A>G (21.17 %). A total of 62 infants (0.58 %) were referred for additional hearing assessments, while 529 (4.92 %) tested positive for genetic mutations (including heterozygous, homozygous, or compound heterozygous variants, as well as mtDNA 12S rRNA homoplasmy), with 522 (4.85 %) passing the hearing screening. Three infants (0.028 %) had two variants in GJB2 (either homozygous or compound heterozygous), and one of these infants passed the newborn hearing test. Additionally, 33 infants (0.307 %) had the MT-RNR1 variant (m.1555A>G or m.1494C>T), all of whom passed the hearing screening. Conclusions The most prevalent mutations associated with deafness were identified as GJB2 c.235delC, SLC26A4 IVS7-2 A>G, and m.1555A>G. The combination of hearing screening and genetic testing for deafness effectively identifies high-risk children with hereditary deafness for further intervention.

Abstract Objectives Neonatal infections, which continue to be a major cause of morbidity and mortality globally, can be avoided with proper umbilical cord care. There is still no widely recognized standard for cord care despite numerous antiseptic techniques, and the hunt for safe, natural, and efficient substitutes is becoming necessary. In this regard, OZOILE, a formulation based on stable ozonides with wound-healing and antibacterial qualities, may be a viable choice. The purpose of this study was to retrospectively assess the impact of topical OZOILE on the timing of umbilical cord detachment and the avoidance or reduction of infection-related problems in newborns. Methods The study was conducted in the Complex Operational Unit of Neonatology and Neonatal Intensive Care of the “Annunziata” Hospital-Cosenza (Italy) and included healthy newborns with a gestational age from the 35th to the 41st weeks of gestation, born to mothers with age ranging from 18 to 40 years. Results Daily application of OZOILE spray oil, directly to the umbilical cord 3 times a day was able the stump fell off in a short time from 5 to 7 days and without any complications. OZOILE reduces secondary alterations of falling umbilical stump. Conclusions In conclusion, OZOILE intervention could be a good candidate for umbilical cord care.

Abstract Objectives To investigate the relationship between serum miR-342, miR-148a, and acute lung injury (ALI) in sepsis patients. Methods A total of 177 sepsis patients were divided into ALI and non-ALI groups; ALI patients were further classified as mild, moderate, or severe. 162 pneumonia patients served as controls. Serum miR-342 and miR-148a levels were measured using RT-qPCR. Results Sepsis patients had lower miR-342 and higher miR-148a than controls (p<0.05). Compared with non-ALI patients, the ALI group showed higher miR-148a, PaCO2, APACHE II scores, and RI, but lower miR-342 and OI (p<0.05). miR-342 decreased and miR-148a increased with ALI severity. Correlation analysis revealed that miR-342 was negatively correlated with PaCO2, APACHE II, and RI, and positively with OI, while miR-148a showed opposite trends. The AUC for predicting ALI using miR-342, miR-148a, and their combination was 0.818, 0.775, and 0.896, respectively. Conclusions Sepsis patients with ALI exhibit low serum miR-342 and high miR-148a, and their combination can effectively predict ALI occurrence.

Abstract Objectives Delirium is a frequent complication in elderly and critically ill patients, associated with significant morbidity and mortality, prolonged hospitalization, increased healthcare costs, and long-term cognitive impairment, emphasizing the need for early identification and prevention strategies. In this study, we aimed to assess the association between pregabalin use and the risk of delirium in elderly intensive care unit (ICU) patients. Methods This retrospective cohort study analyzed data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Propensity score matching (PSM) was applied to control for baseline confounders. Multivariate logistic regression, inverse probability of treatment weighting (IPTW), and subgroup analyses were conducted to validate the findings. Results Out of 12,327 patients, 309 pregabalin users were matched with 1,236 non-users through 1:4 PSM. Pregabalin use was significantly associated with increased delirium risk in patients aged 60 and older, with odds ratios (ORs) of 1.72 (1.31–2.25), 1.90 (1.44–2.49), 1.89 (1.37–2.58), and 1.91 (1.58–2.31) across models. Subgroup analyses confirmed this association across most variables. Notably, the risk was significantly higher among patients not receiving analgesia (p for interaction <0.05). Conclusions Pregabalin use is associated with an elevated risk of delirium in critically ill patients aged 60 and above. These findings have important implications for medication management and delirium prevention in the ICU.

Abstract Objectives Deep vein thrombosis (DVT) demonstrated significant health risk in elderly populations, with numerous comorbidities and biomarkers affecting its incidence. This study evaluated the prevalence, potential allied risk factors for DVT in elderly. Methods A literature search was conducted across PubMed, Science Direct, Cochrane Library, and Google Scholar. After excluding studies, 26 studies were comprised in the study. Data were collected for DVT prevalence and associated risk factors. Results A total of 11,651 participants comprised from China, Japan, Germany, Saudi Arabia, and Thailand. The overall DVT prevalence was 17.10 %, with higher prevalence in females (67.08 %) than males (32.92 %). Age was significantly associated with increased DVT risk (OR=1.54, 95 % CI: 0.34–2.73, p<0.01). While DVT incidence was insignificantly higher among hypertensive and diabetic patients. Significant associations identified between DVT occurrence and malignancy (OR=1.36, 95 % CI: 1.02–1.83, p<0.04), as well as recent surgical history (OR=1.34, 95 % CI: 1.01–1.77, p<0.04). Elevated D-dimer were strongly linked to DVT risk (OR=1.13, 95 % CI: 1.08–1.17, p<0.001). Conclusions This review suggested the significant impact of aging, malignancy, recent surgery, and elevated D-dimer levels on DVT risk in elderly and recommends the assessment of clinical signs, risk factors, and biomarkers in elderly individuals.

Abstract Objectives To evaluate the long-term regulatory effects of high-fiber low-fat (HFLF) diet on gut microbiota diversity and inflammation/barrier-related markers in DSS-induced recurrent colitis mice. Methods A recurrent DSS model was established through multiple cycles of DSS administration. Mice were randomly assigned to HFLF diet vs. control/standard chow ± positive control groups. Multi-timepoint sampling was conducted throughout the study. 16S rRNA sequencing, SCFA quantification, and qPCR/ELISA/immunohistochemistry/Western blot analyses were performed. Results HFLF diet significantly improved clinical phenotype, increased gut microbiota diversity, promoted beneficial bacterial genera, enhanced SCFA production, and modulated inflammation/barrier indicators throughout the recurrence-remission cycles. Conclusions HFLF diet provides sustained protection during recurrence-remission processes through microbiota-SCFA-inflammation axis modulation, offering potential translational applications for IBD management.

Abstract Objectives High altitude poses extreme living environment for humans, impacting human physiology and leading to physiological adaptations, including higher hemoglobin levels in highlanders. However, further understanding is required regarding the medical reference ranges at very high altitudes (>4,500 m). Therefore, we conducted a study involving 1,656 healthy individuals from the “Health Improvement at Very High Altitude (HI-VHA)” population to establish a reference range for 25 biochemical analyses in this population residing at very high altitudes. Methods The HI-VHA project sampled 3,564 individuals from Tibet Autonomous Region above 4,500 m. After strict exclusion criteria, 1,656 healthy individuals were included to establish age and sex stratified reference intervals (RIs) for 25 biochemical analytes using serum samples. Results RIs were generated following the statistical guidelines outlined in CLSI C28-A3. Among the 25 biochemical analytes studied, the levels of ALT, GLB, CREA, UA, HDLC, and HCY showed significant variations by gender, while ALB, AG, CHOL, and DBIL were influenced by age. LDLC was the only analyte affected by both gender and age. AST, TP, TBIL, IBIL, Glu, TG, LDLC, CRP, K, Na, Cl, Ca, Mg, and P, comprising 14 analytes, were not influenced by gender or age. Conclusions We established the RIs for 25 biochemical analytes in the very high-altitude population. These RIs are crucial for disease diagnosis and health management of individuals living at very high altitudes. Moreover, an accurate identification of diseases commonly observed at very high altitudes provides insights into the biological adaptation mechanisms of humans residing in such environments.

Abstract Objectives Coronary artery anomalies are rare both in coronary angiogram and computed tomography angiography. Hypertrophic cardiomyopathy (HCM) is the most frequent inherited cardiac disease. The phenotype of HCM associated with anomalous coronary origin is not commonly seen especially in children. Case presentation We describe a case series of two children with HCM combined right coronary artery (RCA) originated from left coronary sinus. Case 1 was a 9-month-old female with TTN gene heterozygous mutation ( p.R16724L ) who exhibited cardiac insufficiency. Case 2 was a 12-year-old male with MYBPC3 gene heterozygous mutation ( p.R820Q ) who only exhibited intermittent chest pain. A total of 7 HCM cases with RCA originated from left coronary sinus have been reported with our literature review. Case 1 is the youngest child patient in our report until now. Moreover, the echocardiogram of case 1 is similar with restrictive cardiomyopathy (RCM) and it demonstrates the progression of HCM to heart failure. So, HCM with TTN gene mutation may exhibit cardiac insufficiency more early. And the gene mutation site of TTN has never been reported in previous HCM cases. Conclusions HCM coexisted with anomalous origin of RCA has different clinical presentation, and it maybe due to different gene mutation.