This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Liver fibrosis is a vital cause of morbidity in patients with liver diseases and developing novel anti-fibrotic drugs is imperative. Isovalerylspiramycin I (ISP I) as a major component of carrimycin applied to upper respiratory infections, was first found to possess anti-fibrotic potential. The present study aims to evaluate the functions and mechanisms of ISP I in protecting against liver fibrosis. According to our results, ISP I not only reduced the expressions of fibrogenic markers in LX-2 cells but also appeared great protective effects on liver injury and liver fibrosis in bile duct ligation (BDL) rats and carbon tetrachloride (CCl₄) mice. We proved that nucleotide-binding protein 2 (NUBP2) was the direct target of ISP I. ISP I through targeting NUBP2, increased the amount of vascular non-inflammatory molecule-1 (VNN1) on the cell membrane, which will inhibit oxidative stress and fibrosis. Simultaneously, the original carrimycin's protective effect on liver damage and fibrosis was verified. Therefore, our study provides potential agents for patients with liver fibrosis-related diseases, and the clear mechanism supports wide application in the clinic.

The primary role of transfer RNA(tRNA)is to connect a specific amino acid to its 3' end, use its anticodon to match the codon on messenger RNA(mRNA), and deliver the corresponding amino acid to the ribosome for protein synthesis.tRNA exists in two forms: precursor tRNA and mature tRNA.When acted upon by enzymes like Dicer, elaC ribonuclease Z 2(ELAC2), angiopoietin(ANG), and other ribonucleases, tRNA is broken down into tRNA-derived stress-induced RNA(tiRNA)and tRNA-derived fragments(tRF).Recent advancements in RNA sequencing technology have led to increased interest in tiRNA and tRF, shedding light on their roles in various physiological and pathological processes.tRNA-derived small molecules(tsRNA)function similarly to microRNA(miRNA), influencing gene expression and protein synthesis.They show promise as diagnostic markers and potential therapeutic targets for age-related diseases.This review offers a comprehensive analysis of tsRNA classification, biological functions, research advancements, and clinical applications in age-related conditions.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To establish an evaluation model for the radon reduction effect of activated carbon adsorption in localized underground spaces, to guide the rational application of the activated carbon adsorption method for radon reduction in localized underground spaces.Methods:For both intermittent and continuous adsorption-based radon reduction method in localized underground spaces, a theoretical model was constructed for evaluating the of radon reduction effec. By means of this modle, the influence factors on the radon reduction effect were analyzed such as radon concentration, space volume, and air exchange rate with the external environment. Experimental validation of the theoretical model was conducted under typical conditions.Results:The radon exhalation rate from concrete surface in localized underground spaces was inversely linear relationship with the indoor radon concentration. However, the slope of this relationship was very small: when the radon concentration decreased from 2 018 Bq/m 3 to 0, the exhalation rate only increased slightly from 4.20 to 4.46 Bq·m -2·h -1, indicating a minimal change. At the same air exchange rate and in the same space volume, the initial radon concentration had little impact on the adsorption-based radon reduction effect, thus suggesting that the radon generation rate from the enclosure surface could be negligible in the evaluation. In contrast, the adsorption flow rate of a radon reduction device and the air exchange rate between the localized spaces and surrounding environment had significant fluence on radon reduction effect. In the same sealed space and at the same adsorption flow rate, the difference in effect between intermittent and continuous adsorption method was of insignificance. However, in localized spaces with connectivity to surrounding environment, the continuous adsorption significantly outperforms intermittent adsorption, achieving faster radon reduction and better suitability for larger spaces. Simulated experiments validated that the theoretical model for evaluating adsorption-based radon reduction effect was reliable. Conclusions:The research findings provide theoretical guidance on selecting appropriate adsorption-based radon reduction devices for localized underground spaces of different volumes and varing connectivity conditions, in order to reduce the radon concentration within localized spaces to expected levels.

Alzheimer disease(AD)is a neurological disease characterized by cognitive decline.AD continuum refers to the dynamic development progression from early pathological changes to obvious clinical symptoms,covering the continuous spectrum of subjective cognition decline(SCD)stage,mild cognitive impairment(MCI)stage and dementia stage.As one of the key brain regions involved in early stage,hippocampus(HP)in AD continuum is closely related to the progression of disease.MRI has been widely used in the study of HP in the AD continuum.The progresses in structural and functional MRI research of HP changes in AD continuum were reviewed in this article.

Objective To investigate the effect and mechanism of WISP-1 on renal tubular epithelial cell fibrosis in rats with renal fibrosis.Methods Twenty-four adult rats and renal tubular epithelial cell line(NEK-52E)were se-lected for in vivo and in vitro experiments.The rats were randomly divided into control group and study group,and the in vivo renal fibrosis model was established.The expression of WISP-1 in the study group was blocked.The cell lines were induced to fibrosis followed by WISP-1 over-expression or inhibition.The related indicators of fibrosis were observed.Results Protein and mRNA level of Collagen Ⅰ(Col Ⅰ),fibronectin(FN),transforming growth factor-β1(TGF-β1)in WISP-1 over-expression group were all higher than those in control group.The protein and mRNA level of Col Ⅰ,FN and TGF-β1 in the WISP-1 inhibition group were lower than those in the control group(P＜0.05).WISP-1 blockade attenuated the pathological changes of renal fibrosis.The protein and mRNA levels of Col Ⅰ,FN,α-smooth muscle actin(α-SMA),TGF-β1,LC3 and Beclin-1 in the study group were lower than those in the control group,and the level of ubiquitin binding protein p62(SQSTM1/p62)was higher than that in the control group(P＜0.05).The expression of LC3 and Beclin-1 in WISP-1 inhibitor group was lower than that in the control group and the expression of SQSTM1/p62 was higher than that in the control group.The expression of LC3 and Beclin-1 in the WISP-1 over-expression group was higher than that in the control group,and the expres-sion of SQSTM1/p62 was lower than that in the control group.Conclusions Overexpression of WISP-1 promotes the fibrosis of rat renal tubular epithelial cells,and enhanced TGF-β1-mediated autophagy might be a underlying mechanism to mediate renal fibrosis.

Thrombotic diseases refer to a group of conditions characterized by abnormal blood coagulation within blood vessels,leading to the formation of blood clots and a series of clinical symptoms.This includes diseases such as deep vein thrombosis in the lower extremities,stroke,atherosclerosis,and diabetes.Thrombosis is a complex,progressive process that can be broadly summarized as the exposure of vascular endothelial damage,activation of the intrinsic coagulation system,platelet adhesion and aggregation,fibrin network formation,blood cell stasis.Macrophages play an important role in this process.They are involved in local inflammatory responses,regulating both the formation and resolution of thrombi.Macrophage polarization is a hot research topic in recent years,which mainly refers to the morphological and functional changes of macrophages in response different environmental stimuli.Macrophage polarization can be classified into classical(M1)and alternative(M2)types,as well as several specialized polarization states.The transition of macrophage polarization states plays an important role in immune responses,pathogen infections,tumor immunity,and autoimmune processes.This review discusses the regulatory relationship of macrophage polarization in thrombotic diseases,providing new directions for the treatment of these conditions.

Liver fibrosis is a vital cause of morbidity in patients with liver diseases and developing novel anti-fibrotic drugs is imperative.Isovalerylspiramycin Ⅰ(ISP Ⅰ)as a major component of carrimycin applied to upper respiratory infections,was first found to possess anti-fibrotic potential.The present study aims to evaluate the functions and mechanisms of ISP Ⅰ in protecting against liver fibrosis.According to our results,ISP Ⅰ not only reduced the expressions of fibrogenic markers in LX-2 cells but also appeared great protective effects on liver injury and liver fibrosis in bile duct ligation(BDL)rats and carbon tetrachloride(CCl4)mice.We proved that nucleotide-binding protein 2(NUBP2)was the direct target of ISP Ⅰ.ISP Ⅰ through targeting NUBP2,increased the amount of vascular non-inflammatory molecule-1(VNN1)on the cell membrane,which will inhibit oxidative stress and fibrosis.Simultaneously,the original carri-mycin's protective effect on liver damage and fibrosis was verified.Therefore,our study provides po-tential agents for patients with liver fibrosis-related diseases,and the clear mechanism supports wide application in the clinic.

ObjectiveTo investigate the effect and mechanism of Qingre Sanzhuo decoction in treating gouty arthritis （GA） combined with hyperuricaemia （HUA）. MethodsSixty male SD rats were randomized into normal， model， colchicine （0.5 mg·kg^-1）， and low-， medium-， and high-dose （17， 34， 68 g·kg^-1， respectively） Qingre Sanzhuo decoction groups （n=10）. The rats in other groups except the normal group were treated with the modified method for the modeling of GA combined with HUA. The drug intervention groups were administrated with corresponding drugs by gavage in the afternoon every day and the normal group and the model group were administrated with an equal volume of sterile normal saline by gavage. The level of uric acid （SUA） in the serum was measured 2 h after the last administration. The degree of ankle joint swelling was calculated 0.5， 12， 24， 48 h after modeling， and joint inflammation was scored. The pathological changes of ankle joints were observed by hematoxylin-eosin staining， and the serum levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， C reactive protein （CRP）， and interleukin-18 （IL-18） were measured by enzyme-linked immunosorbent assay. Real-time PCR was performed to determine the mRNA levels of NOD-like receptor protein 3 （NLRP3）， apoptosis-associated speck-like protein containing CARD （ASC）， cysteinyl aspartate-specific protease-1 （Caspase-1）， gasdermin D （GSDMD）， and nuclear factor-kappa B （NF-κB） in the synovial tissue of ankle joints. Western blot was employed to determine the protein levels of NLRP3， ASC， and Caspase-1 in ankle joints. The immunohistochemical method was used to detect the expression of GSDMD and NF-κB in the synovial tissue of ankle joints. ResultsCompared with the normal group， the model group showed increased SUA in the serum （P<0.05）， ankle joint swelling and joint inflammation （P<0.05）， increased number of blood vessels in the synovium， inflammatory cell foci in the synovial bursa， elevated serum levels of TNF-α， IL-1β， CRP， and IL-18 （P<0.05）， and up-regulated mRNA and protein levels of NLRP3， ASC， Caspase-1， GSDMD， and NF-κB in the synovial tissue of ankle joints （P<0.05）. Compared with the model group， the medium- and high-dose Qingre Sanzhuo decoction groups showed reduced SUA in the serum （P<0.05）， alleviated ankle joint swelling and joint inflammation （P<0.05）， lowered serum levels of TNF-α， IL-1β， CRP， and IL-18 （P<0.05）， and down-regulated mRNA and protein levels of NLRP3， ASC， Caspase-1， GSDMD， and NF-κB in the synovial tissue of ankle joints （P<0.05）. However， in terms of ameliorating the pathological changes of ankle joints， only the high-dose Qingre Sanzhuo decoction group showed normal morphology of the synovial membrane of ankle joints and no obvious lesion in the articular cartilage. ConclusionQingre Sanzhuo decoction may play a role in preventing and controlling GA combined with HUA by down-regulating the activity of NLRP3/ASC/Caspase-1 pathway and inhibiting the expression of inflammatory cytokines， such as TNF-α， IL-1β， CRP， and IL-18.