Characterization of volatile compounds and sensory properties of spine grape (Vitis davidii Foex) brandies aged with different toasted wood chips.

Aging is an important process for improving wine and brandy quality. In this study, the chemical characterization and sensory properties of spine grape brandies were compared after aging with various species of wood chips, including French oak (FO), American oak (AO), Mongolian oak (MO), Japanese blue oak (JO), chestnut, catalpa, and cherry. The results showed that high color intensity and significant concentrations of tannins and polyphenols were observed in the brandies aged with FO, AO, and chestnut chips. The volatile compounds, such as ethyl decanoate, ethyl 2-methylbutanoate, ethyl octanoate, methyl salicylate, (Z)-2-hexenol, and furfural, contributed to the floral, fruity, and roasted/smoky attributes of the brandies aged with FO, AO, and chestnut chips. The 1-butanol, 1-propanol, phenylethanol, phenylethyl acetate, isoamyl acetate, and linalool contributed to the fruity, honey, and floral attributes of the brandies aged with JO and cherry chips. These findings are extremely useful for the production of differentiated and high-quality spine grape brandies.

Investigating the effects of thermal processing on bitter substances in atemoya (Annona cherimola × Annona squamosa) through sensory-guided separation.

Atemoya (Annona cherimola × Annona squamosa) is a specialty crop in Taiwan. Thermal treatment induces bitterness, complicating seasonal production adjustments and surplus reduction. In this research, sensory-guided separation, metabolomics, and orthogonal partial least squares discrimination analysis (OPLS-DA) are used for identifying the bitterness in atemoya which originates from catechins, epicatechin trimers, and proanthocyanidins. Different thermal treatments (65 °C, 75 °C, and 85 °C) revealed that the glucose and fructose contents in atemoya significantly decreased, while total phenols, flavonoids, and tannins significantly increased. The concentration of 5-hydroxymethylfurfural (5-HMF) increased from 23.16 ng/g in untreated samples to 400.71 ng/g (AP-65), 1208.59 ng/g (AP-75), and 2838.51 ng/g (AP-85). However, these levels are below the 5-HMF bitterness threshold of 3780 ng/g. Combining mass spectrometry analysis with sensory evaluation, OPLS-DA revealed that atemoya treated at 65 °C, 75 °C, and 85 °C exhibited significant bitterness, with the main bitter components being proanthocyanidin dimers and trimers.

Spectroscopic and computational studies of a bifunctional iron- and 2-oxoglutarate dependent enzyme, AsqJ.

Iron and 2-oxoglutarate dependent (Fe/2OG) enzymes exhibit an exceedingly broad reaction repertoire. The most prevalent reactivity is hydroxylation, but many other reactivities have also been discovered in recent years, including halogenation, desaturation, epoxidation, endoperoxidation, epimerization, and cyclization. To fully explore the reaction mechanisms that support such a diverse reactivities in Fe/2OG enzyme, it is necessary to utilize a multi-faceted research methodology, consisting of molecular probe design and synthesis, in vitro enzyme assay development, enzyme kinetics, spectroscopy, protein crystallography, and theoretical calculations. By using such a multi-faceted research approach, we have explored reaction mechanisms of desaturation and epoxidation catalyzed by a bi-functional Fe/2OG enzyme, AsqJ. Herein, we describe the experimental protocols and computational workflows used in our studies.

Genome-wide association study of hypersensitivity skin reactions induced by nonionic iodinated contrast media.

BACKGROUND: In Taiwan, nonionic iodinated contrast media (ICMs) are commonly used but can occasionally cause severe side effects. The infrequency of these adverse events, coupled with the complexities in establishing direct causality, poses significant challenges for genetic research. OBJECTIVE: : To investigate the genetic factors associated with skin reactions mediated by nonionic ICMs on a genome-wide scale. METHODS: A hospital-based cohort from the China Medical University Hospital biobank was utilized to conduct a comprehensive genome-wide association study (GWAS) using PLINK v1.9. The study incorporated two distinct cohorts: one based on adverse drug reaction (ADR) reports, capturing immediate reactions, and the other based on self-reports, which primarily reflected delayed reactions. Known loci were determined by the GWAS catalog. Fine mapping was conducted by FINEMAP to predict causal variants. Pathway enrichment analysis was performed by clusterProfiler to reveal the biological function of the identified genetic signatures. RESULTS: The ADR-based cohort included 120 cases and 3640 controls. GWAS identified 6 candidate risk loci, namely rs150515068, rs6847491, rs192044153, rs191908641, rs376660317, and rs368821335. The self-report-based cohort, consisting of 275 cases and 8338 controls, revealed 36 additional candidate risk loci. Fine mapping further identified 4 causal variants within each cohort. Pathway analysis showed that immediate HSR-related genes are linked to growth hormone response and signaling, while non-immediate HSR genes are involved in neurotransmission. CONCLUSION: This study offers new perspectives on the genetic foundation of nonionic ICM-induced skin reactions within the Taiwanese population, suggesting that the genes contributing to immediate and non-immediate HSRs might have different functional roles.

Systemic toxicity of CAR-T therapy and potential monitoring indicators for toxicity prevention.

Malignant tumors of the hematologic system have a high degree of malignancy and high mortality rates. Chimeric antigen receptor T cell (CAR-T) therapy has become an important option for patients with relapsed/refractory tumors, showing astonishing therapeutic effects and thus, it has brought new hope to the treatment of malignant tumors of the hematologic system. Despite the significant therapeutic effects of CAR-T, its toxic reactions, such as Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), cannot be ignored since they can cause damage to multiple systems, including the cardiovascular system. We summarize biomarkers related to prediction, diagnosis, therapeutic efficacy, and prognosis, further exploring potential monitoring indicators for toxicity prevention. This review aims to summarize the effects of CAR-T therapy on the cardiovascular, hematologic, and nervous systems, as well as potential biomarkers, and to explore potential monitoring indicators for preventing toxicity, thereby providing references for clinical regulation and assessment of therapeutic effects.

The short- and mid-term mortality trends in out-of-hospital cardiac arrest survivors: insights from a 5-year multicenter retrospective study in Taiwan.

Background: The survival trend and factors influencing short- and mid-term mortality in Asian out-of-hospital cardiac arrest (OHCA) survivors should be elucidated. We performed survival analyses on days 3 and 30, hypothesizing decreased survival rates within the initial 3 days post-resuscitation. Additionally, variables linked to mortality at these two timepoints were examined. Methods: We performed a retrospective analysis on adult nontraumatic OHCA survivors admitted to the National Taiwan University Hospital and its branches between 2017 and 2021. We collected the following variables from the NTUH-Integrative Medical Database: basic characteristics, cardiopulmonary resuscitation events, inotrope administration, and post-resuscitation management. The outcomes included 3- and 30-day mortality. Subgroup analyses with the Kaplan-Meier method explored the survival probability of the OHCA survivors and assessed differences in cumulative survival among subgroups. Cox proportional hazards model was used to estimate adjusted hazard ratios with 95% confidence interval. Results: Of the 967 survivors, 273 (28.2%) and 604 (62.5%) died within 3 and 30 days, respectively. The 30-day survival curve after OHCA showed an uneven decline, with the most significant decrease within the first 3 days of admission. Various risk factors influence mortality at 3- and 30-day intervals. Although increased age, noncardiac etiology, and prolonged low-flow time increased mortality risks, bystander CPR, targeted temperature management, and continuous renal replacement therapy were associated with reduced mortality at 3- and 30-day timeframes. Conclusion: Survival declined in most OHCA survivors within 3 days post-resuscitation. The risk factors associated with mortality at 3- and 30-day intervals varied in this population.

Can assessment of human assumed central sensitisation improve the predictive accuracy of the STarT Back screening tool in acute low back pain?

BACKGROUND: The STarT Back Screening Tool (SBT) is recommended to provide risk-stratified care in low back pain (LBP), yet its predictive value is moderate for disability and low for pain severity. Assessment of human assumed central sensitisation (HACS) in conjunction with the SBT may improve its predictive accuracy. OBJECTIVES: To examine whether assessment of HACS in acute LBP improves the predictive accuracy of the SBT for LBP recovery at six months in people with acute non-specific LBP. DESIGN: A prospective longitudinal study. METHOD: Data were drawn from the UPWaRD study. One hundred and twenty people with acute non-specific LBP were recruited from the community. Baseline measures included SBT risk status, nociceptive flexor withdrawal reflex, pressure and heat pain thresholds and conditioned pain modulation. Primary outcome was the presence of LBP (pain numeric rating scale ≥1 and Roland Morris Disability Questionnaire score ≥3) at six-month follow-up. Regression coefficients were penalised using the least absolute shrinkage and selection operator technique to select predictor variables. Internal validation was performed using ten-fold cross-validation. RESULTS/FINDINGS: SBT risk status alone did not predict the presence of LBP at six months (area under receiver operating characteristic curve [AUC] = 0.58). Adding measures of HACS to the SBT did not improve discrimination for whether LBP was present at six months (AUC = 0.59). CONCLUSIONS: This study confirmed the suboptimal predictive accuracy of the SBT, administered during acute LBP, for LBP recovery at six months. Assessment of HACS in acute LBP does not improve the predictive accuracy of the SBT.

Depressive disorders in Chinese left-behind children and adolescents from Yunnan province: prevalence and association with self-harm behaviors.

BACKGROUND: The prevalence of clinically diagnosed depressive disorders (DD) in Chinese left-behind children (LBC) remains unknown. We aim to estimate the prevalence of DD, discuss the associations between DD and self-harm (SH) behaviors in a large representative sample of Chinese LBCs chosen from Yunnan province. METHODS: A total of 5462 LBCs were selected from the most recent datasets of the Mental Health Survey for Children and Adolescents in Yunnan (MHSCAY), a mega population-based two-phase cross-sectional survey. Weighted prevalence rates and designed Logistic regression were adopted to estimate the prevalence of DD and the association between DD and SH. RESULTS: The weighted prevalence of lifetime and current DD were 4.22% (95% CI: 3.13-6.00%) and 3.84% (95% CI: 2.85-5.00%) in Chinese LBCs. Higher lifetime and current DD prevalence rates were observed in girls and those reported adverse parental marital status and SH behaviors. The absence of DD was associated with significantly decreased odds of SH behavior (OR = 0.06), repetitive SH (OR = 0.09), using multiple SH methods (OR = 0.09), and severe SH (OR = 0.15). Subsequently performed stratified analyses identified prominent effect modification by sex and age, as a stronger association between DD and SH was found in girls (OR = 0.02 versus OR = 0.07 in boys) and younger adolescents (OR = 0.08 versus OR = 0.22 in older adolescents). CONCLUSION: The prevalence of DD was high in Chinese LBCs. DD was associated with prominently increased risk of SH behaviors in LBCs. Attention and intervention are needed in this vulnerable population.

The Outcomes of the Initial Misclassification of Undifferentiated Hypotension in the Emergency Department: A Prospective Observational Study.

Background: Managing shock, a life-threatening emergency, is challenging. The influence of the initial misclassification of undifferentiated hypotension (UH) in the emergency department (ED) on patients' outcomes remains uninvestigated. The aim of this study was to investigate whether the initial misclassification of UH in the ED affects patients' clinical outcomes. Materials and Methods: This prospective observational study enrolled 270 non-traumatic adult patients with UH who had visited the ED of National Taiwan University Hospital between July 2020 and January 2022. The patients were divided into same-diagnosis and different-diagnosis groups, depending on the consistency between the initial and final classifications of shock. The outcome was survival to discharge. The clinical variables, management, and outcomes were compared between the groups. Results: A total of 39 of 270 patients (14.4%) were in the different-diagnosis group. Most misclassified patients were initially diagnosed as having hypovolemic shock (HS, n = 29) but finally diagnosed as having distributive shock (DS, n = 28) or cardiogenic shock (n = 1). When compared with the same-diagnosis group, the different-diagnosis group had higher hospitalization (94.9% vs. 81.4%, p = 0.023) but lower ED discharge (5.1% vs. 16.5%, p = 0.046) rates. Logistic regression analysis showed that the HS initially diagnosed was associated with an increased risk of misclassification (odds ratio [OR] = 14.731, 95% confidence interval [CI] = 3.572-60.749, p < 0.001). However, the survival to discharge did not differ between the two groups. DS, when finally diagnosed instead of the initial misclassification, was associated with in-hospital mortality (OR = 0.317, 95%CI = 0.124-0.810, p = 0.016). Conclusions: The misclassification of UH in the ED is not rare, particularly in patients with DS, who are likely to be initially misdiagnosed with HS. Although misclassification may increase hospitalization and decrease ED discharge, it does not affect survival to discharge.

2024 Guidelines of the Taiwan Society of Cardiology on the Primary Prevention of Atherosclerotic Cardiovascular Disease --- Part I.

Atherosclerotic cardiovascular disease (ASCVD) is one of the leading causes of death worldwide and in Taiwan. It is highly prevalent and has a tremendous impact on global health. Therefore, the Taiwan Society of Cardiology developed these best-evidence preventive guidelines for decision-making in clinical practice involving aspects of primordial prevention including national policies, promotion of health education, primary prevention of clinical risk factors, and management and control of clinical risk factors. These guidelines cover the full spectrum of ASCVD, including chronic coronary syndrome, acute coronary syndrome, cerebrovascular disease, peripheral artery disease, and aortic aneurysm. In order to enhance medical education and health promotion not only for physicians but also for the general public, we propose a slogan (2H2L) for the primary prevention of ASCVD on the basis of the essential role of healthy dietary pattern and lifestyles: "Healthy Diet and Healthy Lifestyles to Help Your Life and Save Your Lives". We also propose an acronym of the modifiable risk factors/enhancers and relevant strategies to facilitate memory: " ABC2D2EFG-I'M2 ACE": Adiposity, Blood pressure, Cholesterol and Cigarette smoking, Diabetes mellitus and Dietary pattern, Exercise, Frailty, Gout/hyperuricemia, Inflammation/infection, Metabolic syndrome and Metabolic dysfunction-associated fatty liver disease, Atmosphere (environment), Chronic kidney disease, and Easy life (sleep well and no stress). Some imaging studies can be risk enhancers. Some risk factors/clinical conditions are deemed to be preventable, and healthy dietary pattern, physical activity, and body weight control remain the cornerstone of the preventive strategy.

2024 Update of the TSOC Expert Consensus of Fabry Disease.

As an X-linked inherited lysosomal storage disease that is caused by α-galactosidase A gene variants resulting in progressive accumulation of pathogenic glycosphingolipid (Gb3) accumulation in multiple tissues and organs, Fabry disease (FD) can be classified into classic or late-onset phenotypes. In classic phenotype patients, α-galactosidase A activity is absent or severely reduced, resulting in a more progressive disease course with multi-systemic involvement. Conversely, late-onset phenotype, often with missense variants (e.g., IVS4+919G>A) in Taiwan, may present with a more chronic clinical course with predominant cardiac involvement (cardiac subtype), as they tend to have residual enzyme activity, remaining asymptomatic or clinically silent during childhood and adolescence. In either form, cardiac hypertrophy remains the most common feature of cardiac involvement, potentially leading to myocardial fibrosis, arrhythmias, and heart failure. Diagnosis is established through α-galactosidase enzyme activity assessment or biomarker analyisis (globotriaosylsphingosine, Lyso-Gb3), advanced imaging modalities (echocardiography and cardiac magnetic resonance imaging), and genotyping to differentiate FD from other cardiomyopathy. Successful therapeutic response relies on early recognition and by disease awareness from typical features in classic phenotype and cardiac red flags in cardiac variants for timely therapeutic interventions. Recent advances in pharmacological approach including enzyme replacement therapy (agalsidase alfa or beta), oral chaperone therapy (migalastat), and substrate reduction therapy (venglustat) aim to prevent from irreversible organ damage. Genotype- and gender-based monitoring of treatment effects through biomarker (Lyso-Gb3), renal assessment, and cardiac responses using advanced imaging modalities are key steps to optimizing patient care in FD.

Seminal Vesicle-Derived Exosomes for the Regulation of Sperm Activity.

The seminal vesicle contributes to a large extent of the semen volume and composition. Removal of seminal vesicle or lack of seminal vesicle proteins leads to decreased fertility. Seminal plasma proteome revealed that seminal fluid contained a wide diversity of proteins. Many of them are known to modulate sperm capacitation and serve as capacitation inhibitors or decapacitation factors. Despite identifying secretory vesicles from the male reproductive tract, such as epididymosomes or prostasomes, isolation, identification, and characterization of seminal vesicle-derived exosomes are still unknown. This chapter aims to review the current understanding of the function of seminal vesicles on sperm physiology and male reproduction and provide ultracentrifugation-based isolation protocols for the isolation of seminal vesicle exosomes. Moreover, via proteomic analysis and functional categorization, a total of 726 proteins IDs were identified in the purified seminal vesicle exosomes fraction. Preliminary data showed seminal vesicle-derived exosomes inhibited sperm capacitation; however, more studies will be needed to reveal other functional involvements of seminal vesicle-derived exosomes on the sperm physiology and, more importantly, how these exosomes interact with sperm membrane to achieve their biological effects.

Magnesium-enhanced porcine particles using hydrothermal technique improve the osteogenic differentiation of cells.

Background: Guided bone regeneration (GBR) uses bone grafts and barrier membranes to block soft tissue invasion and eventually create a new bone. Some studies indicate that a porcine bone graft demonstrates excellent biocompatibility and holds promise as a xenograft for GBR. However, only a few studies have investigated the effectiveness of this biomaterial after magnesium coating in improving osteoblast performance. Aim: This study aimed to prove that the hydrothermal method can be used to coat magnesium oxide (MgO) on the surface of a porcine graft and enhance the biomaterial's property for better osteogenic differentiation of osteoblasts in vitro. Materials and Method: A porcine bone graft was produced, and the hydrothermal method was used to coat 2 mM and 5 mM of MgO on the graft. Material physiochemistry and biocompatibility analyses were performed at days 1, 3, and 5. Results: pH value assay results suggested that MgO slightly increased the alkalinity of the graft. SEM images showed that MgO with some surface roughness was coated on the porcine bone surface, and EDX indicated that the Mg and O element percentages increased by about 5% and 9%, respectively. The porcine graft coated with MgO was rougher than an uncoated porcine graft. FTIR analysis of the porcine graft implied that its chemical structure did not change due to MgO hydrothermal processing. Cell viability assay illustrated the highest cell proliferation with the porcine graft with 5 mM MgO (P < 0.001), and good cell attachment was observed on the graft with immunofluorescence using confocal laser scanning microscopy. Cell differentiation assay results revealed that the porcine graft with 5 mM MgO had the highest alkaline phosphate activity (P < 0.0001) among the uncoated porcine graft and the porcine graft with 2 mM MgO. Relative quantitative polymerase chain reaction (qPCR) at days 1 and 5 revealed upregulated osteoblast gene expression with a statistically significant difference. Conclusion: The porcine graft hydrothermally coated with 5 mM MgO was more biocompatible and enhanced osteoblast differentiation. Thus, the findings of this study indicate that a porcine graft with 5 mM MgO has great potential as a bio-bone graft for guided bone regeneration.

The Effect of Novel AI-based Cecum Recognition System on Adenoma Detection Metrics at Screening Colonoscopy Setting.

BACKGROUND AND AIMS: Cecal intubation of colonoscopy relies on self-reporting. We developed an artificial intelligence-based cecum recognition system (AI-CRS) for post hoc verification of cecal intubation and explored its impact on adenoma metrics. METHODS: Quality metrics, including cecal intubation rate (CIR), adenoma detection rate (ADR), and other ADR-related metrics were compared both before (2015-2018) and after (2019-2022) the implementation of AI-CRS. RESULTS: While CIR did not change significantly after the implementation of AI-CRS, ADR and AADR significantly increased. While ADR significantly increased in all segments, the most significant increase in AADR was observed in the proximal colon. Implementation of AI-CRS was associated with a higher likelihood of detecting adenoma (aOR=1.35, 95%CI=1.26-1.45) and advanced adenoma (aOR=1.23, 95%CI=1.07-1.41), respectively. CONCLUSIONS: Implementation of a post hoc verification of cecal intubation using an AI-CRS significantly improved various adenoma metrics in screening colonoscopy.

Cyclopropanation and aziridination catalyzed by non-heme iron and 2-oxoglutarate dependent enzymes.

Cyclopropane and azacyclopropane, also known as aziridine, moieties are found in natural products. These moieties serve as pivotal components that lead to a broad spectrum of biological activities. While diverse strategies involving various classes of enzymes are utilized to catalyze formation of these strained three-membered rings, how non-heme iron and 2-oxoglutarate (Fe/2OG) dependent enzymes enable regio- and stereo-selective C-C and C-N ring closure has only been reported very recently. Herein, we present detailed experimental protocols for mechanistically studying Fe/2OG enzymes that catalyze cyclopropanation and aziridination reactions. These protocols include protein purification, in vitro assays, biophysical spectroscopies, and isotope-tracer experiments. We also report how to use in silico approaches to look for Fe/2OG aziridinases. Furthermore, our current mechanistic understanding of three-membered ring formation is discussed. These results not only shed light on the reaction mechanisms of Fe/2OG enzymes-catalyzed cyclopropanation and aziridination, but also open avenues for expanding the reaction repertoire of the Fe/2OG enzyme superfamily.

Piriformospora indica alleviates soda saline-alkaline stress in Glycine max by modulating plant metabolism.

Soil salinization is one of the major factors limiting agricultural production. Utilizing beneficial microorganisms like Piriformospora indica (P. indica) to enhance plant tolerance to abiotic stresses is a highly effective method, but the influence of P. indica on the growth of soybean in natural saline-alkaline soil remains unclear. Therefore, we investigated the effects of non-inoculation, P. indica inoculation, and fertilization on the growth, antioxidant defense, osmotic adjustment, and photosynthetic gas exchange parameters of soybean under two different levels of saline-alkaline stress in non-sterilized natural saline-alkaline soil. The study found that: 1) P. indica inoculation significantly promoted soybean growth, increasing plant height, root length, and biomass. Under mildly saline-alkaline stress, the increases were 11.5%, 16.0%, and 14.8%, respectively, compared to non-inoculated treatment. Under higher stress, P. indica inoculation achieved the same level of biomass increase as fertilization, while fertilization only significantly improved stem diameter. 2) Under saline-alkaline stress, P. indica inoculation significantly increased antioxidant enzyme activities and reduced malondialdehyde (MDA) content. Under mildly stress, MDA content was reduced by 47.1% and 43.3% compared to non-inoculated and fertilized treatments, respectively. Under moderate stress, the MDA content in the inoculated group was reduced by 29.9% and 36.6% compared to non-inoculated and fertilized treatments, respectively. Fertilization only had a positive effect on peroxidase (POD) activity. 3) P. indica inoculation induced plants to produce more osmotic adjustment substances. Under mildly stress, proline, soluble sugars, and soluble proteins were increased by 345.7%, 104.4%, and 6.9%, respectively, compared to non-inoculated treatment. Under higher stress, the increases were 75.4%, 179.7%, and 12.6%, respectively. Fertilization had no significant positive effect on proline content. 4) With increasing stress, soybean photosynthetic capacity in the P. indica-inoculated treatment was significantly higher than in the non-inoculated treatment, with net photosynthetic rate increased by 14.8% and 37.0% under different stress levels. These results indicate that P. indica can enhance soybean's adaptive ability to saline-alkaline stress by regulating ROS scavenging capacity, osmotic adjustment substance content, and photosynthetic capacity, thereby promoting plant growth. This suggests that P. indica has great potential in improving soybean productivity in natural saline-alkaline soils.

In situ modification of foaming bacterial cellulose with chitosan and its application to active food packaging.

Owing to a lack of specific biological functions, bacterial cellulose (BC) has been restricted in its application to the field of active packaging. In this study, we developed antimicrobial packaging materials using foaming BC (FBC) with chitosan (CS) and applied it to the preservation of chilled sea bass. The material property analysis demonstrated that 1.5 % CS/FBC maintained a high water content of 91 %, a swelling ratio of 75.6 %, great stress of 1.61 MPa, and great strain of 1.87 %. CS incorporation into FBC also decreased its crystallinity from 73.39 % to 69.3 %. Meanwhile, 1.5 % CS/FBC also provided great antimicrobial ability against Escherichia coli and Staphylococcus aureus by approximately 2 log colony-forming units/mL inhibition utilizing contact-killing. Results of the preservation assessment indicated that 1.5 % CS/FBC efficiently inhibited Shewanella putrefaciens growth, reduced total volatile basic nitrogen release, and slightly inhibited lipid oxidation. Based on the above results, CS/FBC is an ecofriendly biomaterial produced from a microorganism that possesses high absorbency and strong antibacterial properties, making it suitable for development as antibacterial active packaging.

Impact of time period and birth cohort on the trend of advanced neoplasm prevalence in the 40-49 average-risk screening population.

BACKGROUND AND AIMS: Early-onset colorectal cancer (CRC) is increasing globally. While the United States have lowered the age of initiation of screening to 45, other countries still start screening at age 50. In Taiwan, the incidence of CRC has declined in 55-74 year-olds after the initiation of screening, but still increased in those 50-54, potentially due to rising precancerous lesion incidence in 40-49 year-olds. This study aimed to explore the chronological trend of the prevalence of colorectal advanced neoplasms (AN) in the screening population aged 40-54. METHODS: We retrospectively analyzed a screening colonoscopy cohort for prevalence of AN in average-risk subjects aged 40-54 from 2003 to 2019. Logistic regression was used to distinguish cohort effect from time-period effect on the prevalence of AN. RESULTS: In total, 27,805 subjects (52.1% male) men were enrolled. There were notable increases in prevalence of AN in all three age groups during the 17-year span, but these were more rapid in age 40-44 (0.99% to 3.22%) and 45-49 (2.50% to 4.19%). Age 50-54 had higher risk of AN [aOR=1.62(1.19-2.19)] in 2003-2008 but not in later periods [2009-2014: aOR=1.08(0.83-1.41)] and [2015-2019: aOR=0.76(0.56-1.03)] when compared with age 45-49. CONCLUSION: The prevalence of AN in age 40-54 increased in the Taiwanese population, with a later birth cohort having a higher prevalence of AN. However, the prevalence of AN in age 45-49 increased more remarkably and approximated that in age 50-54, which may justify earlier initiation of CRC screening at age 45.

Decreased plasma gelsolin fosters a fibrotic tumor microenvironment and promotes chemoradiotherapy resistance in esophageal squamous cell carcinoma.

BACKGROUND: Stromal fibrosis is highly associated with therapeutic resistance and poor survival in esophageal squamous cell carcinoma (ESCC) patients. Low expression of plasma gelsolin (pGSN), a serum abundant protein, has been found to correlate with inflammation and fibrosis. Here, we evaluated pGSN expression in patients with different stages of cancer and therapeutic responses, and delineated the molecular mechanisms involved to gain insight into therapeutic strategies for ESCC. METHODS: Circulating pGSN level in ESCC patients was determined by enzyme-linked immunosorbent assay analysis, and the tissue microarray of tumors was analyzed by immunohistochemistry staining. Cell-based studies were performed to investigate cancer behaviors and molecular mechanisms, and mouse models were used to examine the pGSN-induced tumor suppressive effects in vivo. RESULTS: Circulating pGSN expression is distinctively decreased during ESCC progression, and low pGSN expression correlates with poor therapeutic responses and poor survival. Methylation-specific PCR analysis confirmed that decreased pGSN expression is partly attributed to the hypermethylation of the GSN promoter, the gene encoding pGSN. Importantly, cell-based immunoprecipitation and protein stability assays demonstrated that pGSN competes with oncogenic tenascin-C (TNC) for the binding and degradation of integrin αvß3, revealing that decreased pGSN expression leads to the promotion of oncogenic signaling transduction in cancer cells and fibroblasts. Furthermore, overexpression of pGSN caused the attenuation of TNC expression and inactivation of cancer-associated fibroblast (CAF), thereby leading to tumor growth inhibition in mice. CONCLUSIONS: Our results demonstrated that GSN methylation causes decreased secretion of pGSN, leading to integrin dysregulation, oncogenic TNC activation, and CAF formation. These findings highlight the role of pGSN in therapeutic resistance and the fibrotic tumor microenvironment of ESCC.

Ceftazidime-avibactam: Combination therapy versus monotherapy in the challenge of pneumonia caused by carbapenem-resistant Klebsiella pneumoniae.

This research focused on evaluating the clinical results of patients suffering from pneumonia caused by carbapenem-resistant Klebsiella pneumoniae (CRKP), who received treatment with either ceftazidime-avibactam (CZA) alone or in combination with other antibiotics. From January 2020 to December 2023, we retrospectively analyzed CRKP-related pneumonia patients treated in two Chinese tertiary hospitals. Mortality was measured at 14 and 30 days as the primary outcome. Secondary outcomes included the 14-day microbiological cure rate and the 14-day clinical cure rate. Factors contributing to clinical failure were evaluated via both univariate analysis and multivariate logistic regression. To account for confounding factors, propensity score matching (PSM) was utilized. Among the 195 patients with CRKP infections, 103 (52.8 %) received CZA combination therapy, and 92 (47.2 %) patients received CZA monotherapy. The combination therapy group exhibited superior clinical and microbiological cure rates compared to the monotherapy group, with a 14-day clinical cure rate of 60.1 % vs. 45.7 % (P = 0.042) and a 14-day microbiological cure rate of 72.8 % vs. 58.6 % (P = 0.038), respectively. Combination therapy reduced mortality rates at 14 days (7.8 % vs. 17.4 %, P = 0.041), but not at 30 days (14.6 % vs. 25.0 %, P = 0.066). Even after using PSM, the group treated with the CZA combination continued to had a lower mortality rate at 14 days (5.9 % vs. 17.6 %, P = 0.039). The 14-day clinical cure rate for the combination therapy group was 63.2 %, and the 14-day microbial cure rate was 77.9 %. Both of these statistics were notably greater than those observed in the monotherapy group. Furthermore, the multivariate logistic regression model indicated a significant link between combination therapy and a decrease in clinical failure. Carbapenems were noted to be the most effective class of concomitant agents. Our findings indicate that patients with pneumonia due to CRKP benefit from combination treatment of CZA rather than monotherapy; administering carbapenem in combination with CZA in the early stages could provide considerable survival benefits.