OBJECTIVE To investigate the mechanism of isochlorogenic acid A against hepatocellular carcinoma based on the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway and multi-omics technology. METHODS The invasion rate and migration rate of human hepatocellular carcinoma HepG2 cells after 48 h of intervention with 0 （control group）， 0.25 and 0.5 mg/mL isochlorogenic acid A were examined； mRNA expression of DEP domain-containing mTOR-interacting protein （DEPTOR）， the protein expressions of mTOR， PI3K and phosphatase and tensin homologue deleted on chromosome ten （PTEN）， as well as the phosphorylation level of Akt protein were determined in the cells. Metabolomics analysis was performed using liquid chromatography-tandem mass spectrometry， and differential metabolites were screened and subjected to Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis； transcriptomics monitoring was conducted by RNA sequencing， and differentially expressed genes were screened and subjected to gene ontology （GO） and KEGG pathway enrichment analyses. RESULTS Compared with the control group， intervention with 0.25 and 0.5 mg/mL isochlorogenic acid A for 48 h significantly inhibited the invasion rate and migration rate of HepG2 cells， significantly up-regulated the mRNA expression of DEPTOR and the protein expression of PTEN， and significantly down-regulated the protein expression of PI3K and the phosphorylation level of Akt protein （except for 0.25 mg/mL isochlorogenic acid A） （ P ＜0.05）. A total of 304 differential metabolites and 212 differentially expressed genes were screened by multi-omics analysis. KEGG pathway enrichment analysis suggested that isochlorogenic acid A regulated key signaling of HepG2 cell growth mainly by inhibiting the PI3K/Akt signaling pathway， synergizing with metabolic reprogramming such as mTOR signaling pathway， ferroptosis， pentose phosphate pathway and purine/pyrimidine metabo lism. CONCLUSIONS The anti-hepatocellular carcinoma effect of isochlorogenic acid A is associated with the blockade of abnormal activation of the PI3K/Akt/mTOR signaling pathway. In addition， it may also be related to the inhibition of the pentose phosphate pathway and purine/pyrimidine metabolism， as well as the induction of ferroptosis，etc.

Background/Aims: Chronic constipation is prevalent yet under-diagnosed across Asia, compromising quality of life and burdening healthcare systems. Cultural stigma, varied diets, and limited access to standardized diagnostic tools delay timely care. Methods: The Bali Chronic Constipation Roundtable in November 2024, brought together experts from 11 Asian countries. The group reviewed epidemiological data, analyzed multinational questionnaire on clinical practice pattern, and conducted structured discussions to identify key barriers and propose region-specific recommendations. Results: Chronic constipation prevalence varies across Asia, ranging from 1.8% in India to 16.6% in Japan, with women and the elderly disproportionately affected. Under-reporting persists owing to cultural taboos and widespread self treatment with laxatives and traditional medications. Although the Rome IV criteria remains the global standard, they may not fully reflect Asian symptom profiles, and diagnosis is limited by scarce motility laboratories. First line therapies such as dietary-fiber optimization and osmotic laxatives are widely available, but newer pharmacotherapies (prucalopride, linaclotide, lubiprostone, and elobixibat) remain costly and unevenly accessible. Biofeedback for dyssynergic defecation is underutilized due to limited availability. Experts recommend expanded regional research on to refine diagnostic criteria, coupled with enhanced physician education and public awareness. They advocate accessibility to second-line and novel therapies that incorporate culturally attuned regional guidelines, and improved access to gastrointestinal motility testing. Conclusions The Bali Chronic Constipation Roundtable highlighted Asia’s need for region specific diagnostics and management. Addressing diagnostic and treatment gaps will improve outcomes, while ongoing researcher clinician policy collaboration must standardize guidelines, advance research, and ensure equitable care across Asia.

Background: This study was performed to characterize the incidence, costs, and risk factors associated with renal and cardiovascular adverse outcomes following primary percutaneous coronary intervention (pPCI) in patients with ST-elevation myocardial infarction (STEMI). Methods: Patients with STEMI who underwent pPCI using iso-osmolar contrast were enrolled at 39 centers. The incidence of acute kidney injury (AKI) and major adverse renal and cardiovascular events (MARCE) was analyzed, as well as inpatient costs. Logistic regression analysis was performed to identify risk factors. Results: Among 2,293 patients, the incidence of AKI and MARCE within 72 hours post-pPCI was 4.14% (n = 95) and 4.40% (n = 101), respectively. AKI and/or MARCE were associated with systolic blood pressure (AKI: odds ratio [OR], 1.009; 95% confidence interval [CI], 1.000–1.018), hypertension (AKI: OR, 1.815; 95% CI, 1.133–2.906; MARCE: OR, 1.760;95% CI, 1.118–2.769), anterior wall infarction (AKI: OR, 1.895; 95% CI, 1.196–3.004; MARCE:OR, 1.939; 95% CI, 1.240–3.032), Killip class (AKI: OR, 1.465; 95% CI, 1.117–1.922; MARCE:OR, 1.467; 95% CI, 1.131–1.903), and serum creatinine (SCr; MARCE: OR, 1.006; 95% CI, 1.000–1.012). Hospitalization costs for patients with STEMI who developed AKI or MARCE were significantly higher than for those without AKI (9,595 ± 5,795 vs. 8,279 ± 3,872 USD, P = 0.003) or without MARCE (9,890 ± 5,616 vs. 8,255 ± 3,859 USD, P < 0.001). Conclusions In patients with STEMI undergoing pPCI with iso-osmolar contrast, the incidence of AKI and MARCE was associated with higher hospitalization costs. Systolic blood pressure, hypertension, anterior wall infarction, Killip class, and SCr were identified as risk factors for these outcomes.

In the context of burgeoning economic trade, there has been a remarkable increase in the number of ships travelling between domestic and international ports. Inbound and outbound cargo ships, cruise liners, ferries, and other types of vessels have emerged as critical vehicles for the dispersal of vector organisms and the spread of infectious disease agents. Public health concerns associated with these vessels represent a significant threat to human welfare. In this paper, we comprehensively review the hazards posed by vector organisms on ships, the latest advances in prevention and control strategies, and proposes appropriate countermeasures. The aim is to provide effective guidance for the prevention and control of public health security issues caused by ship-borne vector organisms.

Background: Visual impairment is increasingly prevalent, underscoring the need for effective prevention strategies. This study investigated the association between cardiovascular health and visual impairment using three progressively developed metrics: Life’s Simple 7 (LS7), a cardiovascular health score developed by the American Heart Association based on 7 components, including physical activity, smoking status, body mass index (BMI), diet, blood glucose, blood pressure, and total cholesterol; Life’s Essential 8(LE8), which adds sleep health as an additional component; and Life’s Crucial 9 (LC9), which further incorporates mental health. We aimed to evaluate whether these expanded metrics provide additional explanatory value and to inform future public health strategies. Objective: To investigate the associations among LS7, LE8, and LC9 cardiovascular health scores and visual impairment in National Health and Nutrition Examination Survey 2013 to 2018, assess the added value of sleep and mental health components, and identify key contributing subcomponents using regression and machine learning methods. Methods: We analyzed data from 9891 participants in the 2013 to 2018 National Health and Nutrition Examination Survey. Multivariable logistic regression, restricted cubic spline modeling, and subgroup analyses were conducted to evaluate the association between cardiovascular health and visual impairment. Machine learning methods, including Random Forest and SHapley Additive exPlanations, a model interpretation approach used to assess feature importance, were applied. The Boruta algorithm, a feature selection method, was used to identify key subcomponents of cardiovascular health. Results: Participants with visual impairment were older, had lower poverty-to-income ratios, and exhibited lower cardiovascular health scores (LS7, LE8, and LC9). Higher cardiovascular health scores were negatively associated with visual impairment. Each one standard deviation increase in LS7, LE8, and LC9 was associated with approximately 8%, 2%, and 3% lower odds of visual impairment, respectively. LS7 showed the strongest negative association, whereas LE8 and LC9 emerged as the most important predictors in the machine learning models. Key subcomponents such as blood glucose, blood pressure, and BMI, as well as mental health status, were strongly associated with visual impairment. Conclusion: Higher cardiovascular health scores were negatively associated with visual impairment. LS7 demonstrated the strongest statistical association, whereas LE8 and LC9 were the most influential features in the machine learning models. Blood glucose, blood pressure, BMI, and mental health status were important correlates of visual impairment. From the perspective of the “prevention and treatment of diseases” in traditional Chinese medicine and the holistic concept, the aforementioned research findings confirm that severe visual impairment is indeed an external manifestation of overall health imbalance (such as organ dysfunction and Qi deficiency and blood stasis). The prevention strategy lies in comprehensively adjusting lifestyle, emotional factors, and metabolic indicators (corresponding to the key factors in the study) to restore the body’s internal balance and achieve prevention before disease arises.

Lung cancer is the most common malignant tumor worldwide, ranking first in both incidence and mortality rates. According to the latest statistics from the International Agency for Research on Cancer (IARC), approximately 2.5 million new cases and around 1.8 million deaths from lung cancer occurred in 2022, placing a tremendous burden on global healthcare systems. The high mortality rate of lung cancer is closely linked to its subtle early symptoms, which often lead to diagnosis at advanced stages. This not only complicates treatment but also results in substantial economic losses. Current treatment options for lung cancer include surgery, radiotherapy, chemotherapy, targeted drug therapy, and immunotherapy. Among these, immunotherapy has emerged as the most groundbreaking advancement in recent years, owing to its unique antitumor mechanisms and impressive clinical benefits. Unlike traditional therapies such as radiotherapy and chemotherapy, immunotherapy activates or enhances the patient’s immune system to recognize and eliminate tumor cells. It offers advantages such as more durable therapeutic effects and relatively fewer toxic side effects. The main approaches to lung cancer immunotherapy include immune checkpoint inhibitors, tumor-specific antigen-targeted therapies, adoptive cell therapies, cancer vaccines, and oncolytic virus therapies. Among these, immune checkpoint inhibitors and tumor-specific antigen-targeted therapies have received approval from the U.S. Food and Drug Administration (FDA) for clinical use in lung cancer, significantly improving outcomes for patients with advanced non-small cell lung cancer. Although other immunotherapy strategies are still in clinical trials, they show great potential in improving treatment precision and efficacy. This article systematically reviews the latest research progress in lung cancer immunotherapy, including the development of novel immune checkpoint molecules, optimization of treatment strategies, identification of predictive biomarkers, and findings from recent clinical trials. It also discusses the current challenges in the field and outlines future directions, such as the development of next-generation immunotherapeutic agents, exploration of more effective combination regimens, and the establishment of precise efficacy prediction systems. The aim is to provide a valuable reference for the continued advancement of lung cancer immunotherapy.

OBJECTIVE: To assess the independent and combined effects of air pollutants, meteorological factors, and greenspace exposure on new tuberculosis (TB) cases. METHODS: TB case data from Shanghai (2013-2018) were obtained from the Shanghai Center for Disease Control and Prevention. Environmental data on air pollutants, meteorological variables, and greenspace exposure were obtained from the National Tibetan Plateau Data Center. We employed a distributed-lag nonlinear model to assess the effects of these environmental factors on TB cases. RESULTS: Increased TB risk was linked to PM _2.5, PM ₁₀, and rainfall, whereas NO ₂, SO ₂, and air pressure were associated with a reduced risk. Specifically, the strongest cumulative effects occurred at various lags: PM _2.5 ( RR = 1.166, 95% CI: 1.026-1.325) at 0-19 weeks; PM ₁₀ ( RR = 1.167, 95% CI: 1.028-1.324) at 0-18 weeks; NO ₂ ( RR = 0.968, 95% CI: 0.938-0.999) at 0-1 weeks; SO ₂ ( RR = 0.945, 95% CI: 0.894-0.999) at 0-2 weeks; air pressure ( RR = 0.604, 95% CI: 0.447-0.816) at 0-8 weeks; and rainfall ( RR = 1.404, 95% CI: 1.076-1.833) at 0-22 weeks. Green space exposure did not significantly impact TB cases. Additionally, low temperatures amplified the effect of PM _2.5 on TB. CONCLUSION Exposure to PM _2.5, PM ₁₀, and rainfall increased the risk of TB, highlighting the need to address air pollutants for the prevention of TB in Shanghai.
China/epidemiology* ; Humans ; Air Pollutants/analysis* ; Tuberculosis/epidemiology* ; Incidence ; Meteorological Concepts ; Particulate Matter/adverse effects* ; Environmental Exposure ; Male ; Female ; Adult ; Air Pollution ; Middle Aged

OBJECTIVE: CRISPR-Cas protects bacteria from exogenous DNA invasion and is associated with bacterial biofilm formation and pathogenicity. METHODS: We analyzed the type I-F CRISPR-Cas system of Legionella pneumophila WX48, including Cas1, Cas2-Cas3, Csy1, Csy2, Csy3, and Cas6f, along with downstream CRISPR arrays. We explored the effects of the CRISPR-Cas system on the in vitro growth, biofilm-forming ability, and pathogenicity of L. pneumophila through constructing gene deletion mutants. RESULTS: The type I-F CRISPR-Cas system did not affect the in vitro growth of wild-type or mutant strains. The biofilm formation and intracellular proliferation of the mutant strains were weaker than those of the wild type owing to the regulation of type IV pili and Dot/Icm type IV secretion systems. In particular, Cas6f deletion strongly inhibited these processes. CONCLUSION The type I-F CRISPR-Cas system may reduce biofilm formation and intracellular proliferation in L. pneumophila.
Legionella pneumophila/pathogenicity* ; CRISPR-Cas Systems ; Biofilms/growth & development* ; Phenotype ; Bacterial Proteins/metabolism* ; Gene Deletion

Objective:To explore the value of non-invasive habitat imaging (HI) multi-parametric MRI (mpMRI) in predicting the risk of prostate cancer (PCa).Methods:In this cross-sectional study, 220 patients with PCa confirmed by radical prostatectomy (RP) who underwent multi-parametric MRI (mpMRI) scanning at Xijing Hospital, Air Force Military Medical University from January 2018 to May 2024 were retrospectively collected. Patients were divided into a training set (154 cases) and a test set (66 cases) by simple random sampling in a 7∶3 ratio. Based on mpMRI imaging, the apparent diffusion coefficient (ADC), perfusion fraction (f), and mean kurtosis (MK) of each voxel were integrated. The K-means clustering algorithm was used to divide the PCa target lesions into habitat subregions, generate habitat maps, and calculate the proportion of each habitat subregion in the entire lesion. According to the 2019 International Society of Urological Pathology (ISUP) guidelines, patients were categorized into a low-risk group (ISUP≤2, 65 cases) and a high-risk group (ISUP≥3, 155 cases). The RP specimens were matched with the habitat map to identify corresponding habitat subregions, and the ISUP grade of each subregion was individually evaluated to calculate the detection rate of high-risk PCa patients. The logistic regression analysis was applied to identify the independent risk factors associated with PCa risk, and the HI-clinical imaging model and clinical imaging model were constructed. The efficacy of the models was assessed using receiver operating characteristic curve.Results:Based on the optimal cluster number, the habitat was divided into three subregions. Habitat 1 had lower ADC and f values and higher MK values, while habitat 2 had the opposite characteristics, and habitat 3 was intermediate. The proportion of habitat 1 in the high-risk group was 28.8%, in the low-risk group was 8.9%. In the training set, the comparison of habitat subregions with pathological results showed that the detection rate of high-risk lesions was 66.9% (103/154) in habitat 1, 25.3% (39/154) in habitat 2, and 47.4% (73/154) in habitat 3. The logistic regression analysis indicated that the proportion of habitat 1 ( OR=3.03, 95% CI 1.77-5.18, P<0.001), prostate-specific antigen ( OR=1.66, 95% CI 1.04-2.66, P=0.034), and the prostate imaging reporting and data system score ( OR=1.65, 95% CI 1.00-2.70, P=0.048) as independent risk factors for high-risk PCa. In the training set, the area under the curve (AUC) for predicting PCa risk was 0.854 (95% CI 0.789-0.920) for the HI-clinical imaging model and 0.779 (95% CI 0.701-0.856) for the clinical imaging model. In the test set, the AUC values were 0.809 (95% CI 0.693-0.895) and 0.738 (95% CI 0.619-0.856), respectively. Conclusion:HI based on mpMRI can effectively predict the risk of PCa.