Objective To investigate the biological activity of raddeanin A(RA) against nasopharyngeal carcinoma(NPC)and the molecular mechanism of anti-NPC mediated by ERK/MAPK signaling pathway.Methods CCK-8 assay was used to detect the inhibitory effect of RA on the growth of NPC cells. Bioinformatics was utilized to predict the targets of RA acting on NPC and their associated signaling pathways. The binding affinity between RA and core target was analyzed by molecular docking. Annexin V-FITC/PI, JC-1 staining, flow cytometry, combined with Western blot were used to further investigate the anti-proliferation mechanism of RA in NPC cells.Results RA effectively inhibited the proliferation of NPC cell lines 6-10B and 5-8F, with IC_(50)values of 5. 770 and 5. 068 ??mol/L, respectively. The pharmacological effects were primarily associated with cell apoptosis and the MAPK signaling pathway. The binding affinities between RA and core target proteins, such as MAPK1 and caspase 3, predicted through molecular docking, were less than-5 kcal/mol. RA induced apoptosis and mitochondrial membrane potential changes in 6-10B cells. The expression levels of apoptosis-related proteins, including cleaved PARP, cleaved caspase 3, and cleaved caspase 9, significantly increased(F = 229. 60, 136. 60 and 73. 67, P < 0. 001,< 0. 001 and < 0. 01, respectively). Additionally, the expression of the mitochondrial pathway-related protein Bax was marked-ly upregulated, while Bcl-2 expression was significantly downregulated(F = 47. 42 and 17. 54, P < 0. 001 and P < 0. 05,respectively). Furthermore, the expression levels of ERK/MAPK pathway-related proteins, including p-p90 RSK, p-ERK1/2,and p-MSK1, were significantly reduced(F = 106. 90, 27. 73 and 101. 50, P < 0. 05, < 0. 01 and < 0. 05, respectively).Conclusion RA regulates the ERK/MAPK signaling pathway, reduces mitochondrial membrane potential, triggers mitochondrial pathway to induce apoptosis, and then exerts the activity of inhibiting NPC cell proliferation.

Purpose: This study aimed to project cancer incidence and mortality for 2025 to estimate Korea’s current cancer burden. Materials and Methods: Cancer incidence data from 1999 to 2022 were obtained from the Korea National Cancer Incidence Database, while cancer mortality data from 1993 to 2023 were acquired from Statistics Korea. Cancer incidence and mortality were projected by fitting a linear regression model to observed age-specific cancer rates against their respective years and then by multiplying the projected age-specific rates by the anticipated age-specific population for 2025. A joinpoint regression model was applied to identify significant changes in trends, using only the most recent trend data for predictions. Results: A total of 304,754 new cancer cases and 84,019 cancer deaths are expected in Korea in 2025. The most commonly diagnosed cancer is projected to be thyroid cancer, followed by the colorectal, lung, breast, prostate and stomach cancers. These six cancers are expected to account for 63.8% of the total cancer burden. Lung cancer is expected to be the leading cause of cancer-related deaths, followed by liver, colorectal, pancreatic, stomach, and gallbladder cancers, together comprising 66.6% of total cancer deaths. Conclusion The increasing incidence of female breast cancer and the rise in prostate and pancreatic cancers are expected to continue. As aging accelerates, cancer commonly found in older adults are projected to rise significantly.

Purpose: The current study provides national cancer statistics and their secular trends in Korea, including incidence, mortality, survival, and prevalence in 2022, with international comparisons. Materials and Methods: Cancer incidence, survival, and prevalence rates were calculated using the Korea National Cancer Incidence Database (1999-2022), with survival follow-up until December 31, 2023. Mortality data obtained from Statistics Korea, while international comparisons were based on GLOBOCAN data. Results: In 2022, 282,047 newly diagnosed cancer cases (age-standardized rate [ASR], 287.0 per 100,000) and 83,378 deaths from cancer (ASR, 65.7 per 100,000) were reported. The proportion of localized-stage cancers increased from 45.6% in 2005 to 50.9% in 2022. Stomach, colorectal, and breast cancer showed increased localized-stage diagnoses by 18.1, 18.5, and 9.9 percentage points, respectively. Compared to 2001-2005, the 5-year relative survival (2018-2022) increased by 20.4 percentage points for stomach cancer, 7.6 for colorectal cancer, and 5.6 for breast cancer. Korea had the lowest cancer mortality among countries with similar incidence rates and the lowest mortality-to-incidence (M/I) ratios for these cancers. The 5-year relative survival (2018-2022) was 72.9%, contributing to over 2.59 million prevalent cases in 2022. Conclusion Since the launch of the National Cancer Screening Program in 2002, early detection has improved, increasing the diagnosis of localized-stage cancers and survival rates. Korea recorded the lowest M/I ratio among major comparison countries, demonstrating the effectiveness of its National Cancer Control Program.

Purpose: This study aimed to project cancer incidence and mortality for 2025 to estimate Korea’s current cancer burden. Materials and Methods: Cancer incidence data from 1999 to 2022 were obtained from the Korea National Cancer Incidence Database, while cancer mortality data from 1993 to 2023 were acquired from Statistics Korea. Cancer incidence and mortality were projected by fitting a linear regression model to observed age-specific cancer rates against their respective years and then by multiplying the projected age-specific rates by the anticipated age-specific population for 2025. A joinpoint regression model was applied to identify significant changes in trends, using only the most recent trend data for predictions. Results: A total of 304,754 new cancer cases and 84,019 cancer deaths are expected in Korea in 2025. The most commonly diagnosed cancer is projected to be thyroid cancer, followed by the colorectal, lung, breast, prostate and stomach cancers. These six cancers are expected to account for 63.8% of the total cancer burden. Lung cancer is expected to be the leading cause of cancer-related deaths, followed by liver, colorectal, pancreatic, stomach, and gallbladder cancers, together comprising 66.6% of total cancer deaths. Conclusion The increasing incidence of female breast cancer and the rise in prostate and pancreatic cancers are expected to continue. As aging accelerates, cancer commonly found in older adults are projected to rise significantly.

Purpose: The current study provides national cancer statistics and their secular trends in Korea, including incidence, mortality, survival, and prevalence in 2022, with international comparisons. Materials and Methods: Cancer incidence, survival, and prevalence rates were calculated using the Korea National Cancer Incidence Database (1999-2022), with survival follow-up until December 31, 2023. Mortality data obtained from Statistics Korea, while international comparisons were based on GLOBOCAN data. Results: In 2022, 282,047 newly diagnosed cancer cases (age-standardized rate [ASR], 287.0 per 100,000) and 83,378 deaths from cancer (ASR, 65.7 per 100,000) were reported. The proportion of localized-stage cancers increased from 45.6% in 2005 to 50.9% in 2022. Stomach, colorectal, and breast cancer showed increased localized-stage diagnoses by 18.1, 18.5, and 9.9 percentage points, respectively. Compared to 2001-2005, the 5-year relative survival (2018-2022) increased by 20.4 percentage points for stomach cancer, 7.6 for colorectal cancer, and 5.6 for breast cancer. Korea had the lowest cancer mortality among countries with similar incidence rates and the lowest mortality-to-incidence (M/I) ratios for these cancers. The 5-year relative survival (2018-2022) was 72.9%, contributing to over 2.59 million prevalent cases in 2022. Conclusion Since the launch of the National Cancer Screening Program in 2002, early detection has improved, increasing the diagnosis of localized-stage cancers and survival rates. Korea recorded the lowest M/I ratio among major comparison countries, demonstrating the effectiveness of its National Cancer Control Program.

Background/Aims: Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population. Methods: This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019). Results: Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg. Conclusions In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.

Background/Aims: Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population. Methods: This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019). Results: Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg. Conclusions In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.

Delirium is a common cause and complication of hospitalization in the elderly and is associated with higher risk of future dementia and progression of existing dementia, of which 70% is Alzheimer's disease (AD). AD and delirium, which are known to be aggravated by one another, represent significant societal challenges, especially in light of the absence of effective treatments. The intricate biological mechanisms have led to numerous clinical trial setbacks and likely contribute to the limited efficacy of existing therapeutics. Artificial intelligence (AI) presents a promising avenue for overcoming these hurdles by deploying algorithms to uncover hidden patterns across diverse data types. This review explores the pivotal role of AI in revolutionizing drug discovery for AD and delirium from target identification to the development of small molecule and protein-based therapies. Recent advances in deep learning, particularly in accurate protein structure prediction, are facilitating novel approaches to drug design and expediting the discovery pipeline for biological and small molecule therapeutics. This review concludes with an appraisal of current achievements and limitations, and touches on prospects for the use of AI in advancing drug discovery in AD and delirium, emphasizing its transformative potential in addressing these two and possibly other neurodegenerative conditions.

Five new flavan-4-ol glycosides jixueqiosides A-E (1-5) and two new flavan glycosides jixueqiosides F and G (6 and 7), along with twelve known flavan-4-ol glycosides (8-19), were isolated from the roots of Pronephrium penangianum. Comprehensive spectral analyses, X-ray single-crystal diffraction, and theoretical electronic circular dichroism (ECD) calculations established structures and absolute configurations. A single crystal structure of flavan-4-ol glycoside (14) was reported for the first time, while the characteristic ECD and NMR data for all isolated flavan-4-ol glycosides (1-5 , 8-19) were analyzed, establishing a set of empirical rules. Activity screening of these isolates showed that 8 and 9 could inhibit the proliferation of MDA-MB-231 and MCF-7 cells with IC₅₀ values of 7.93 ? 2.85 ?mol?L^-1 and 5.87 ? 1.58 ?mol?L^-1 (MDA-MB-231), and 2.21 ? 1.38 ?mol?L^-1 and 3.52 ? 1.55 ?mol?L^-1 (MCF-7), respectively. Western blotting and flow cytometry analyses demonstrated that 8 and 9 dose-dependently induced apoptosis in MDA-MB-231 cells by up-regulating BAX, activating caspase-3 and down-regulating BCL-2. Additionally, compound 8 affected autophagy-related proteins, increasing the ratio of LC3-II/LC3-I and Beclin-1 levels to inhibit MDA-MB-231 cell proliferation. Moreover, anti-inflammatory studies indicated that 2, 3, 7, 13, 14, and 18 moderately inhibited tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), and nitric oxide (NO) release.
Humans ; Plant Roots/chemistry* ; Glycosides/isolation & purification* ; Anti-Inflammatory Agents/isolation & purification* ; Flavonoids/isolation & purification* ; Cell Proliferation/drug effects* ; Antineoplastic Agents, Phytogenic/isolation & purification* ; Molecular Structure ; Apoptosis/drug effects* ; Cell Line, Tumor ; Tumor Necrosis Factor-alpha/immunology* ; Drugs, Chinese Herbal/pharmacology* ; Interleukin-6/immunology* ; Animals ; Mice

Chiropractic therapy is a therapeutic approach for regulating the spine and is widely employed in clinical practice for multiple disorders, including constipation. The theory of "bone strengthening and tendon softening" originated from Huang Di Nei Jing, holding that bones maintain normal anatomical forms and relative positional relationships, and tendons are supple and free from damage. Only when the structures and functions of both are normal can the human body sustain normal physiological activities. In accordance with this theory, clinical treatment mainly aims at adjusting the relationship between tendons and bones and restoring the balance between them to address diseases. Based on the theory of "bone strengthening and tendon softening" and taking the essence of "tendons" as the starting point, this article explored the pathogenic mechanism of outlet obstructive constipation and the clinical application of chiropractic therapy in the treatment of outlet obstructive constipation. Pathological changes of the musculotendinous meridians and abnormal spinal structures are significant pathogenic factors for outlet obstructive constipation. Therefore, in clinical practice, spinal techniques such as guided manipulation, massage, and reconstructive techniques can be used to soften muscles, correct bones, and regulate intestinal stagnation.